AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This mul...AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.展开更多
AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopa...AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022.Women with BC who are menopausal were found to have an OM incidence of 1.6%.Furthermore,CA-153,CA-125,and apolipoprotein A(Apo A)all contributed to OM in women with BC who are postmenopausal according to binary logistic regression.Receiver operating curve(ROC)analysis was used to assess the diagnostic value of OM in patients with BC.RESULTS:Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%,whereas CA-153+Apo A illustrated the highest specificity of 99.02%.Moreover,CA-153 and CA-153+CA-125 had higher areas under the curve(AUC)of 0.973.CONCLUSION:The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC.The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.展开更多
AIM:To evaluate the efficacy and safety of intravitreal low-dose(1 mg)triamcinolone acetonide(TA)in Chinese acute nonarteritic anterior ischemic optic neuropathy(NAION)patients.METHODS:Twenty-eight eyes of 28 patients...AIM:To evaluate the efficacy and safety of intravitreal low-dose(1 mg)triamcinolone acetonide(TA)in Chinese acute nonarteritic anterior ischemic optic neuropathy(NAION)patients.METHODS:Twenty-eight eyes of 28 patients with acute NAION(<30d of visual acuity loss)were enrolled and given intravitreal TA(IVTA)once.Visual field(VF),best corrected visual acuity(BCVA),retinal nerve fiber layer(RNFL)thickness,ganglion cell complex(GCC)thickness,radial peripapillary capillary(RPC)density,and intraocular pressure(IOP)were evaluated at baseline and 7d,1,3,and 6mo after IVTA.RESULTS:VF and BCVA were significant improved during the follow-up according to the mean deviation(MD),visual field index(VFI),and Early Treatment Diabetic Retinopathy Study(ETDRS)scores(all P<0.001).There was no significant difference between the group that received an injection less than 14d after illness onset and the group that received an injection more than 14d after illness onset.The RNFL thickness,GCC thickness and RPC density were significantly decreased(all P<0.001).Temporary ocular hypertension was present in five eyes.CONCLUSION:Low-dose IVTA may be an alternative safe treatment option for some NAION patients in the acute stage.However,optic nerve atrophy still existed.展开更多
Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as ...Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.展开更多
AIM: To explore the performance in diabetic retinopathy(DR) screening of artificial intelligence(AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional table...AIM: To explore the performance in diabetic retinopathy(DR) screening of artificial intelligence(AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera(Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR.RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range(1.47, 1.48, and 1.40) than conventional tabletop cameras(1.30, 1.28, and 1.18;P<0.001). Detection of retinal hemorrhage, hard exudation,and macular edema were comparable between the two modalities, in principle, with the area under the curve of the handheld fundus camera slightly lower. The sensitivity and specificity for the detection of referable DR with the handheld camera were 82.1%(95%CI: 72.1%-92.2%) and 97.4%(95%CI: 95.4%-99.5%), respectively. The performance of AI detection of DR using the Phoebus Algorithm was satisfactory;however, Phoebus showed a high sensitivity(88.2%, 95%CI: 79.4%-97.1%) and low specificity(40.7%, 95%CI: 34.1%-47.2%) when detecting referable DR.CONCLUSION: The handheld Aurora fundus camera combined with autonomous AI system is well-suited in DR screening without mydriasis because of its high sensitivity of DR detection as well as its image quality, but its specificity needs to be improved with better modeling of the data. Use of this new system is safe and effective in the detection of referable DR in real world practice.展开更多
AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHO...AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.展开更多
AIM:To investigate changes in local brain activity after laser assisted in situ keratomileusis(LASIK)in myopia patients,and further explore whether post-LASIK(POL)patients and healthy controls(HCs)can be distinguished...AIM:To investigate changes in local brain activity after laser assisted in situ keratomileusis(LASIK)in myopia patients,and further explore whether post-LASIK(POL)patients and healthy controls(HCs)can be distinguished by differences in dynamic amplitude of low-frequency fluctuations(dALFF)in specific brain regions.METHODS:The resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 15 myopic patients who underwent LASIK and 15 matched healthy controls.This method was selected to calculate the corresponding dALFF values of each participant,to compare dALFF between the groups and to determine whether dALFF distinguishes reliably between myopic patients after LASIK and HCs using the linear support vector machine(SVM)permutation test(5000 repetitions).RESULTS:dALFF was lower in POL than in HCs at the right precentral gyrus and right insula.Classification accuracy of the SVM was 89.1%(P<0.001).CONCLUSION:The activity of spontaneous neurons in the right precentral gyrus and right insula of myopic patients change significantly after LASIK.SVM can correctly classify POL patients and HCs based on dALFF differences.展开更多
AIM:To assess the alterations in the resting-state function connections between the two cerebral hemispheres in patients with optic neuritis(ON)and healthy controls(HCs).METHODS:A total of 12 ON patients(six males and...AIM:To assess the alterations in the resting-state function connections between the two cerebral hemispheres in patients with optic neuritis(ON)and healthy controls(HCs).METHODS:A total of 12 ON patients(six males and six females)and 12 HCs(six males and six females)who were highly matched for sex,age,and educational level were recruited.They underwent functional magnetic resonance imaging(fMRI),testing and brain activities were assessed using the degree centrality(DC)method.Correlation analysis between the mean DC values in specific brain areas and behavior performances was analyzed as well.Linear correlations between A anxiety scale(AS)and depression scale(DS)values and DC values in brain regions of patients with ON were also analyzed.RESULTS:The areas that showed a higher DC value in ON patients were the right angular gyrus and bilateral precuneus,while the left insula and left superior temporal gyrus(LSTG)were regions that presented a lower DC value in ON patients.A receiver operating characteristic(ROC)curve analysis confirmed the accuracy of the area under the curve(AUC)assessment.Linear analysis showed anxiety scale(AS)and depression scale(DS)values in the left insula were both negatively correlated with DC values,while best corrected visual acuity logMAR-R(BCVA logMAR-R)showed a negative correlation with DC in the LSTG.CONCLUSION:The study explores altered brain activities of specific regions in patients with ON.The results provide clues for revealing the underlying mechanism of ON development.展开更多
AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimenta...AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimental PVR was induced by intravitreal injection of retinal pigment epithelium（RPE） cells in the eyes of rabbits. A PI3 K/Akt inhibitor（wortmannin） and a GSK3β inhibitor（Li Cl） were also injected at different time during PVR progress. Electroretinogram（ERG）, ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling（TUNEL） assay. The vitreous was also collected for metabolomic analysis. RESULTS： Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION： GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.展开更多
AIM:To explore the photopic pupil size behavior in myopic children undergoing overnight orthokeratology(ortho-k)over 1-year period and its effects on the axial elongation.METHODS:A total of 202 Chinese myopic children...AIM:To explore the photopic pupil size behavior in myopic children undergoing overnight orthokeratology(ortho-k)over 1-year period and its effects on the axial elongation.METHODS:A total of 202 Chinese myopic children were enrolled in this prospective clinical trial.Ninetyfive subjects in ortho-k group and eighty-eight subjects in spectacle group completed the 1-year study.Axial length(AL)was measured before enrollment and every 6mo after the start of ortho-k.The photopic pupil diameter(PPD)was determined using the Pentacam AXL and measured in an examination room with lighting of 300-310 Lx.Stepwise multiple linear regression analysis was used to identify variables contribution to axial elongation.RESULTS:Compared with spectacle group,the average 1-year axial elongation was significantly slower in the ortho-k group(0.25±0.27 vs 0.44±0.23 mm,P<0.0001).In ortho-k group,PPDs significantly decreased from 4.21±0.62 mm to 3.94±0.53 mm after 1mo of lens wear(P=0.001,Bonferroni correction)and the change lasts for 3-month visit.No significantly change during the other follow-up visits was found(P>0.05,Bonferroni correction).The 4.81 mm PPD may be a possible cutoff point in the ortho-k group.Subjects with PPD below or equal to 4.81 mm tended to have smaller axial elongation compared to subjects with PPD above 4.81 mm after 1-year period(t=-3.09,P=0.003).In ortho-k group,univariate analyses indicated that those with older age,greater degree of myopia,longer AL,smaller baseline PPD(PPDbaseline)experienced a smaller change in AL.In multivariate analyses,older age,greater AL and smaller PPDbaseline were associated with smaller increases in AL.In spectacle group,PPD tended to be stable(P>0.05,Bonferroni correction)and did not affect axial growth.CONCLUSION:PPDs experience significantly decreases at 1-month and 3-month ortho-k treatment.Children with smaller PPD tend to experience slower axial elongation and may benefit more from ortho-k.展开更多
AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identi...AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identify potential new treatment targets and strategies.METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at-80℃ and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS.RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [plateletderived growth factor(PDGF)-AA, glial cell line-derived neurotrophic factor(GDNF), and vascular endothelial growth factor A(VEGFA)], inflammatory mediators [interleukin(IL)-8, IL-11, and tumor necrosis factor-α(TNF-α)] and cytokines [chemokine C-X-C ligand(CXCL)10, interferon-γ(IFN-γ), and granulocyte macrophage-colony stimulating factor(GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group(all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not(P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls(P>0.05).CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.展开更多
Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more ...Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels.The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated.The diabetic condition facilitates epigenetic changes and influences target gene expression.In this review,we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.展开更多
AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injecti...AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin.The retinas were harvested at 1 to 24 wk after diabetes onset.Hypoxia-treated mouse microglial cell line(BV2 cells)was employed as the in vitro model to mimic diabetic condition.The expressions of Iba-1,CD11 b,ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction,Western blot and immunofluorescence both in vivo and in vitro.RESULTS:Compared with age-matched normal control,the number of microglia(Iba-1 positive immunostaining)in diabetic rat retinas was increased from 1 to 24 wk of diabetes,which was most obvious at 12 wk of diabetes.Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control;however,there was statistically significant between two groups only at 2 wk after diabetes onset.The m RNA expression of Iba-1 was decreased significantly at 2 and 4 wk of diabetic rat retinas,and remained unchanged at 8 and 12 wk of diabetes.In BV2 cells,there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups;however,its m RNA level was decreased significantly under hypoxia.To further characterize microglial activation,F4/80,CD11 b and inflammatory factors were detected both in vivo and in vitro.Compared with normal control,the expressions of F4/80 and CD11 b as well as the inflammatory factors,such as ICAM-1,i NOS,COX2,IL-1βand IL-6,were increased significantly both in vivo and in vitro.CONCLUSION:Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR.However,Iba-1 immunostaining,in combination with other markers like CD11 b and ICAM-1,could be well reflect the activation of microglia.Thus,it is of great importance to explore other potential marker to evaluate the activation of microglia.展开更多
AIM： To compare the clinical performance of 4 spectraldomain（SD） optical coherence tomography angiography（OCTA） systems： AngioVueTM, AngioPlexTM, Spectralis？ OCTA, AngioScan, and 1 swept-source（SS） OCTA SS OC...AIM： To compare the clinical performance of 4 spectraldomain（SD） optical coherence tomography angiography（OCTA） systems： AngioVueTM, AngioPlexTM, Spectralis？ OCTA, AngioScan, and 1 swept-source（SS） OCTA SS OCT AngioTM. METHODS： Twenty-seven undilated right eyes of 27 participants underwent OCTA examination using five different systems respectively for both 3×3 and 6×6 mm^2 scan pattern（Spectralis OCTA for 3×3 mm^2 scan only）. Image quality, including vessel valid visibility and the number of motion artifacts, and acquisition time were evaluated. Repeated measures analysis of variance（ANOVA） with Bonferroni＇s post-test and Friedman test with Dunn＇s posttest were used to compare measurements.RESULTS： The age of the subjects was 28.19±5.55 y（range, 23-49 y）. The spherical equivalent refraction was-2.55±1.84 D（range, 0.00 to-5.25 D）. Significant difference was observed in the evaluation of vessel valid visibility（Angio Vue the highest： 0.111±0.031 for 3×3 mm^2 scan and 0.128±0.020 for 6×6 mm^2 scan）, number of motion artifacts（AngioVue the fewest： 0.778±1.086 for 3×3 mm^2 scan and 0.333±0.620 for 6×6 mm^2 scan） and acquisition time（AngioPlex the shortest： 8.537±1.921 s for 3×3 mm^2 scan and 8.298±1.741 s for 6×6 mm^2 scan; all P〈0.001）. CONCLUSION： There is poor agreement of measurements among systems. AngioVue provides images with the highest vessel valid visibility and the fewest motion artifacts. AngioPlex achieves the shortest acquisition.展开更多
AIM:To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial(hES-RPE)cells in vitro,and compare the behaviors and functions of h...AIM:To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial(hES-RPE)cells in vitro,and compare the behaviors and functions of h ESRPE cells on two culture substrates,laminin521(LN-521)and truncated recombinant human vitronectin(VTN-N).METHODS:hES-RPE cells were used in the experiment.The abilities of LN-521 and VTN-N at different concentrations to adhere to hES-RPE cells were compared with a high-content imaging system.Quantitative real-time polymerase chain reaction was used to evaluate RPE-specific gene expression levels midway(day 10)and at the end(day 20)of the time course.Cell polarity was observed by immunofluorescent staining for apical and basal markers of the RPE.The phagocytic ability of hES-RPE cells was identified by flow cytometry and immunofluorescence.RESULTS:The cell adhesion assay showed that the ability of LN-521 to adhere to hES-RPE cells was dosedependent.With increasing coating concentration,an increasing number of cells attached to the surface of LN-521-coated wells.In contrast,VTN-N presented a strong adhesive ability even at a low concentration.The optimal concentration of LN-521 and VTN-N required to coat and adhesion to hES-RPE cells were 2 and 0.25μg/cm^(2),respectively.Furthermore,both LN-521 and VTN-N could facilitate adoption of the desired cobblestone cellular morphology with tight junction and showed polarity by the hES-RPE cells.However,hES-RPE cells cultivated in VTN-N had a greater phagocytic ability,and it took less time for these hES-RPE cells to mature.CONCLUSION:VTN-N is a more suitable coating substrate for cultivating hES-RPE cells.展开更多
AIM：To explore the roles of phospholipids and sphingolipids in the inflammatory process of uveitis.METHODS：Aqueous humor（AH） and the retina were obtained from endotoxin-induced uveitis（EIU） rats during the acute...AIM：To explore the roles of phospholipids and sphingolipids in the inflammatory process of uveitis.METHODS：Aqueous humor（AH） and the retina were obtained from endotoxin-induced uveitis（EIU） rats during the acute inflammation stage（24 h after endotoxin injection）.Lipids were extracted using a modified Bligh and Dyer method and subjected to mass spectrometric identification using class-specific lipid standards and ratiometric quantification.Relative intensity analysis was performed to evaluate the amount change of common lipids between the EIU and control groups.RESULTS：Unique lipid species encompassing all five phospholipid classes were found in both control and the EIU AH and retina.Commensurate with the significantly increased level of lysophospholipids in the EIU AH and retina,we found that the ratio of lysophospholipids to total phospholipids was significantly increased too.We also detected a significant increase in 18：0 lysophosphatidylcholine levels in the EIU group（fold change =6.4 in AH and 3.8 in retina）.Cer240,Cer241,and SM240 levels remarkably increased in the EIU AH.Enhanced C12 ceramide-1-phosphate（C12 C-1-P）,C16 C-1-P,C24 C-1-P,and upregulated Cer160,Cer240,SM120,and SM240 were found in EIU retina.C-1-P was believed to restore homeostasis by inhibiting nuclear factor kappa B（NF-κB） activation.However,we still found elevated NF-κB levels in the EIU retina.CONCLUSION：A variety of lipids might have played a critical role in EIU inflammation.Exogenous topical application of these protective lipids or inhibition of these pro-inflammatory lipids may be useful therapeutic strategies for the resolution of EIU.展开更多
AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical cohe...AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical coherence tomography angiography(OCTA).METHODS: RDVCI patients and gender-and agematched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density(PFVD) of retinal deep vascular complex(DVC), ICP, and DCP were analyzed, and the percentage of reduction(PR) of PFVD was calculated.RESULTS: Twenty-four eyes in 22 RDVCI patients(20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls(DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%;chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%;chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%;chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%;all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase(P=0.812), but significant difference in chronic phase(P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC(P=0.735) or ICP(P=0.681) was found, but significant difference in the DCP(P=0.041).CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.展开更多
In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alte...In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.展开更多
AIM:To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane(ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis(MF).METHODS:A 23-gauge 3-por...AIM:To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane(ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis(MF).METHODS:A 23-gauge 3-port pars plana vitrectomy was performed on 16 patients with high MF.A parallel arc line along the vascular arcades was scraped out with a curved membrane scraper DSP.Next,an ILM forceps was used to catch hold of the incisal edge of the ILM flap,and the action of releasing and separating was subsequently taken toward the direction of the macular fovea.Next,the ILM forceps was used to grasp the released area,and the whole area coherent ILM peeling covering the macular fovea was implemented thereafter.Finally,the ILM was folded backwards and peeled off in the arc direction.RESULTS:At the final visit,the average central macular thickness decreased remarkably from 423.76±177.67 to 178.24±66.21 μm.The mean logarithm of the minimum angle of resolution best-corrected visual acuity of 1.37±0.59 was significantly alleviated to 0.74±0.59.CONCLUSION:The wide range of whole piece consecutive ILM peeling without preservation of the epifovea is proven to be effective and significantly reduced the occurrence of retinal tear and macular hole.展开更多
●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A to...●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.展开更多
基金Supported by the Program of Shanghai Academic/Technology Research Leader(No.21XD1402700)the Clinical Research Plan of Shenkang Hospital Development Center of Shanghai(No.SHDC2022CRD001).
文摘AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Jiangxi Key R&D Program of Jiangxi Province(No.20223BBH80014)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2022B258)Science and Technology Project of Jiangxi Health Commission(No.202210017).
文摘AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022.Women with BC who are menopausal were found to have an OM incidence of 1.6%.Furthermore,CA-153,CA-125,and apolipoprotein A(Apo A)all contributed to OM in women with BC who are postmenopausal according to binary logistic regression.Receiver operating curve(ROC)analysis was used to assess the diagnostic value of OM in patients with BC.RESULTS:Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%,whereas CA-153+Apo A illustrated the highest specificity of 99.02%.Moreover,CA-153 and CA-153+CA-125 had higher areas under the curve(AUC)of 0.973.CONCLUSION:The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC.The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.
基金Supported by the National Key R&D Program of China(No.2016YFC0904800,No.2019YFC0840607)the National Science and Technology Major Project of China(No.2017ZX09304010)the Clinical Research Innovation Plan of Shanghai General Hospital(No.CTCCR-2018BP04).
文摘AIM:To evaluate the efficacy and safety of intravitreal low-dose(1 mg)triamcinolone acetonide(TA)in Chinese acute nonarteritic anterior ischemic optic neuropathy(NAION)patients.METHODS:Twenty-eight eyes of 28 patients with acute NAION(<30d of visual acuity loss)were enrolled and given intravitreal TA(IVTA)once.Visual field(VF),best corrected visual acuity(BCVA),retinal nerve fiber layer(RNFL)thickness,ganglion cell complex(GCC)thickness,radial peripapillary capillary(RPC)density,and intraocular pressure(IOP)were evaluated at baseline and 7d,1,3,and 6mo after IVTA.RESULTS:VF and BCVA were significant improved during the follow-up according to the mean deviation(MD),visual field index(VFI),and Early Treatment Diabetic Retinopathy Study(ETDRS)scores(all P<0.001).There was no significant difference between the group that received an injection less than 14d after illness onset and the group that received an injection more than 14d after illness onset.The RNFL thickness,GCC thickness and RPC density were significantly decreased(all P<0.001).Temporary ocular hypertension was present in five eyes.CONCLUSION:Low-dose IVTA may be an alternative safe treatment option for some NAION patients in the acute stage.However,optic nerve atrophy still existed.
基金supported by the National Natural Science Foundation of China,No. 82171062 (to JFZ)。
文摘Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.
基金Supported by the National Natural Science Foundation of China(No.81970845)European Union’s Horizon 2020 research and innovation programme under grant agreement(No.778089)。
文摘AIM: To explore the performance in diabetic retinopathy(DR) screening of artificial intelligence(AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera(Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR.RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range(1.47, 1.48, and 1.40) than conventional tabletop cameras(1.30, 1.28, and 1.18;P<0.001). Detection of retinal hemorrhage, hard exudation,and macular edema were comparable between the two modalities, in principle, with the area under the curve of the handheld fundus camera slightly lower. The sensitivity and specificity for the detection of referable DR with the handheld camera were 82.1%(95%CI: 72.1%-92.2%) and 97.4%(95%CI: 95.4%-99.5%), respectively. The performance of AI detection of DR using the Phoebus Algorithm was satisfactory;however, Phoebus showed a high sensitivity(88.2%, 95%CI: 79.4%-97.1%) and low specificity(40.7%, 95%CI: 34.1%-47.2%) when detecting referable DR.CONCLUSION: The handheld Aurora fundus camera combined with autonomous AI system is well-suited in DR screening without mydriasis because of its high sensitivity of DR detection as well as its image quality, but its specificity needs to be improved with better modeling of the data. Use of this new system is safe and effective in the detection of referable DR in real world practice.
基金Supported by the National Natural Science Foundation of China(No.82171076,No.U22A20311,No.82388101)the National Key R&D Program(No.2022YFC2502800)Shanghai Municipal Education Commission(No.2023KJ05-67).
文摘AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.
基金Supported by National Natural Science Foundation of China(No.82160195No.82460203)Key R&D Program of Jiangxi Province(No.20223BBH80014).
文摘AIM:To investigate changes in local brain activity after laser assisted in situ keratomileusis(LASIK)in myopia patients,and further explore whether post-LASIK(POL)patients and healthy controls(HCs)can be distinguished by differences in dynamic amplitude of low-frequency fluctuations(dALFF)in specific brain regions.METHODS:The resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 15 myopic patients who underwent LASIK and 15 matched healthy controls.This method was selected to calculate the corresponding dALFF values of each participant,to compare dALFF between the groups and to determine whether dALFF distinguishes reliably between myopic patients after LASIK and HCs using the linear support vector machine(SVM)permutation test(5000 repetitions).RESULTS:dALFF was lower in POL than in HCs at the right precentral gyrus and right insula.Classification accuracy of the SVM was 89.1%(P<0.001).CONCLUSION:The activity of spontaneous neurons in the right precentral gyrus and right insula of myopic patients change significantly after LASIK.SVM can correctly classify POL patients and HCs based on dALFF differences.
基金Supported by National Natural Science Foundation of China(No.82160195No.82460203)Key R&D Program of Jiangxi Province(No.20223BBH80014).
文摘AIM:To assess the alterations in the resting-state function connections between the two cerebral hemispheres in patients with optic neuritis(ON)and healthy controls(HCs).METHODS:A total of 12 ON patients(six males and six females)and 12 HCs(six males and six females)who were highly matched for sex,age,and educational level were recruited.They underwent functional magnetic resonance imaging(fMRI),testing and brain activities were assessed using the degree centrality(DC)method.Correlation analysis between the mean DC values in specific brain areas and behavior performances was analyzed as well.Linear correlations between A anxiety scale(AS)and depression scale(DS)values and DC values in brain regions of patients with ON were also analyzed.RESULTS:The areas that showed a higher DC value in ON patients were the right angular gyrus and bilateral precuneus,while the left insula and left superior temporal gyrus(LSTG)were regions that presented a lower DC value in ON patients.A receiver operating characteristic(ROC)curve analysis confirmed the accuracy of the area under the curve(AUC)assessment.Linear analysis showed anxiety scale(AS)and depression scale(DS)values in the left insula were both negatively correlated with DC values,while best corrected visual acuity logMAR-R(BCVA logMAR-R)showed a negative correlation with DC in the LSTG.CONCLUSION:The study explores altered brain activities of specific regions in patients with ON.The results provide clues for revealing the underlying mechanism of ON development.
基金Supported by the National Natural Science Foundation of China(No.81371039)Shanghai Natural Science Foundation(No.18ZR1440200)
文摘AIM： To investigate the regulatory mechanism of glycogen synthase kinase 3β（GSK3β） in epithelialmesenchymal transition（EMT） process after proliferative vitreoretinopathy（PVR） induction. METHODS： Experimental PVR was induced by intravitreal injection of retinal pigment epithelium（RPE） cells in the eyes of rabbits. A PI3 K/Akt inhibitor（wortmannin） and a GSK3β inhibitor（Li Cl） were also injected at different time during PVR progress. Electroretinogram（ERG）, ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling（TUNEL） assay. The vitreous was also collected for metabolomic analysis. RESULTS： Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION： GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.
基金Supported by the Natural Science Foundation of Shanghai(No.18ZR1435700)Clinical Research Project of Shanghai Health and Family Planning Committee(No.201840199)。
文摘AIM:To explore the photopic pupil size behavior in myopic children undergoing overnight orthokeratology(ortho-k)over 1-year period and its effects on the axial elongation.METHODS:A total of 202 Chinese myopic children were enrolled in this prospective clinical trial.Ninetyfive subjects in ortho-k group and eighty-eight subjects in spectacle group completed the 1-year study.Axial length(AL)was measured before enrollment and every 6mo after the start of ortho-k.The photopic pupil diameter(PPD)was determined using the Pentacam AXL and measured in an examination room with lighting of 300-310 Lx.Stepwise multiple linear regression analysis was used to identify variables contribution to axial elongation.RESULTS:Compared with spectacle group,the average 1-year axial elongation was significantly slower in the ortho-k group(0.25±0.27 vs 0.44±0.23 mm,P<0.0001).In ortho-k group,PPDs significantly decreased from 4.21±0.62 mm to 3.94±0.53 mm after 1mo of lens wear(P=0.001,Bonferroni correction)and the change lasts for 3-month visit.No significantly change during the other follow-up visits was found(P>0.05,Bonferroni correction).The 4.81 mm PPD may be a possible cutoff point in the ortho-k group.Subjects with PPD below or equal to 4.81 mm tended to have smaller axial elongation compared to subjects with PPD above 4.81 mm after 1-year period(t=-3.09,P=0.003).In ortho-k group,univariate analyses indicated that those with older age,greater degree of myopia,longer AL,smaller baseline PPD(PPDbaseline)experienced a smaller change in AL.In multivariate analyses,older age,greater AL and smaller PPDbaseline were associated with smaller increases in AL.In spectacle group,PPD tended to be stable(P>0.05,Bonferroni correction)and did not affect axial growth.CONCLUSION:PPDs experience significantly decreases at 1-month and 3-month ortho-k treatment.Children with smaller PPD tend to experience slower axial elongation and may benefit more from ortho-k.
基金Supported by the National Natural Science Foundation of China (No.82101132,No.81800878)。
文摘AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identify potential new treatment targets and strategies.METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at-80℃ and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS.RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [plateletderived growth factor(PDGF)-AA, glial cell line-derived neurotrophic factor(GDNF), and vascular endothelial growth factor A(VEGFA)], inflammatory mediators [interleukin(IL)-8, IL-11, and tumor necrosis factor-α(TNF-α)] and cytokines [chemokine C-X-C ligand(CXCL)10, interferon-γ(IFN-γ), and granulocyte macrophage-colony stimulating factor(GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group(all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not(P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls(P>0.05).CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.
基金supported by the National Natural Science Foundation of China,No.82171062(to JFZ)Aier Eye Hospital Group Scientific Research Fund,No.AF2101D8(to LMG).
文摘Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels.The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated.The diabetic condition facilitates epigenetic changes and influences target gene expression.In this review,we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.
基金Supported by National Natural Science Foundation of China(No.81570852)。
文摘AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin.The retinas were harvested at 1 to 24 wk after diabetes onset.Hypoxia-treated mouse microglial cell line(BV2 cells)was employed as the in vitro model to mimic diabetic condition.The expressions of Iba-1,CD11 b,ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction,Western blot and immunofluorescence both in vivo and in vitro.RESULTS:Compared with age-matched normal control,the number of microglia(Iba-1 positive immunostaining)in diabetic rat retinas was increased from 1 to 24 wk of diabetes,which was most obvious at 12 wk of diabetes.Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control;however,there was statistically significant between two groups only at 2 wk after diabetes onset.The m RNA expression of Iba-1 was decreased significantly at 2 and 4 wk of diabetic rat retinas,and remained unchanged at 8 and 12 wk of diabetes.In BV2 cells,there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups;however,its m RNA level was decreased significantly under hypoxia.To further characterize microglial activation,F4/80,CD11 b and inflammatory factors were detected both in vivo and in vitro.Compared with normal control,the expressions of F4/80 and CD11 b as well as the inflammatory factors,such as ICAM-1,i NOS,COX2,IL-1βand IL-6,were increased significantly both in vivo and in vitro.CONCLUSION:Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR.However,Iba-1 immunostaining,in combination with other markers like CD11 b and ICAM-1,could be well reflect the activation of microglia.Thus,it is of great importance to explore other potential marker to evaluate the activation of microglia.
基金Supported by National Key Research and Development Program for Precision Medicine of China (No.2016YFC0904800)
文摘AIM： To compare the clinical performance of 4 spectraldomain（SD） optical coherence tomography angiography（OCTA） systems： AngioVueTM, AngioPlexTM, Spectralis？ OCTA, AngioScan, and 1 swept-source（SS） OCTA SS OCT AngioTM. METHODS： Twenty-seven undilated right eyes of 27 participants underwent OCTA examination using five different systems respectively for both 3×3 and 6×6 mm^2 scan pattern（Spectralis OCTA for 3×3 mm^2 scan only）. Image quality, including vessel valid visibility and the number of motion artifacts, and acquisition time were evaluated. Repeated measures analysis of variance（ANOVA） with Bonferroni＇s post-test and Friedman test with Dunn＇s posttest were used to compare measurements.RESULTS： The age of the subjects was 28.19±5.55 y（range, 23-49 y）. The spherical equivalent refraction was-2.55±1.84 D（range, 0.00 to-5.25 D）. Significant difference was observed in the evaluation of vessel valid visibility（Angio Vue the highest： 0.111±0.031 for 3×3 mm^2 scan and 0.128±0.020 for 6×6 mm^2 scan）, number of motion artifacts（AngioVue the fewest： 0.778±1.086 for 3×3 mm^2 scan and 0.333±0.620 for 6×6 mm^2 scan） and acquisition time（AngioPlex the shortest： 8.537±1.921 s for 3×3 mm^2 scan and 8.298±1.741 s for 6×6 mm^2 scan; all P〈0.001）. CONCLUSION： There is poor agreement of measurements among systems. AngioVue provides images with the highest vessel valid visibility and the fewest motion artifacts. AngioPlex achieves the shortest acquisition.
基金Supported by the National Natural Science Foundation of China(No.81730026No.81970816)+2 种基金the National Key R&D Program(No.2017YFA0105301)Science and Technology Commission of Shanghai Municipality(No.20Z11900400No.19495800700)。
文摘AIM:To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial(hES-RPE)cells in vitro,and compare the behaviors and functions of h ESRPE cells on two culture substrates,laminin521(LN-521)and truncated recombinant human vitronectin(VTN-N).METHODS:hES-RPE cells were used in the experiment.The abilities of LN-521 and VTN-N at different concentrations to adhere to hES-RPE cells were compared with a high-content imaging system.Quantitative real-time polymerase chain reaction was used to evaluate RPE-specific gene expression levels midway(day 10)and at the end(day 20)of the time course.Cell polarity was observed by immunofluorescent staining for apical and basal markers of the RPE.The phagocytic ability of hES-RPE cells was identified by flow cytometry and immunofluorescence.RESULTS:The cell adhesion assay showed that the ability of LN-521 to adhere to hES-RPE cells was dosedependent.With increasing coating concentration,an increasing number of cells attached to the surface of LN-521-coated wells.In contrast,VTN-N presented a strong adhesive ability even at a low concentration.The optimal concentration of LN-521 and VTN-N required to coat and adhesion to hES-RPE cells were 2 and 0.25μg/cm^(2),respectively.Furthermore,both LN-521 and VTN-N could facilitate adoption of the desired cobblestone cellular morphology with tight junction and showed polarity by the hES-RPE cells.However,hES-RPE cells cultivated in VTN-N had a greater phagocytic ability,and it took less time for these hES-RPE cells to mature.CONCLUSION:VTN-N is a more suitable coating substrate for cultivating hES-RPE cells.
基金Supported by the National Natural Science Foundation of China(No.81300776)the Youth Scientific Research Project of Shanghai Municipal Health Bureau(No.20134Y088)
文摘AIM：To explore the roles of phospholipids and sphingolipids in the inflammatory process of uveitis.METHODS：Aqueous humor（AH） and the retina were obtained from endotoxin-induced uveitis（EIU） rats during the acute inflammation stage（24 h after endotoxin injection）.Lipids were extracted using a modified Bligh and Dyer method and subjected to mass spectrometric identification using class-specific lipid standards and ratiometric quantification.Relative intensity analysis was performed to evaluate the amount change of common lipids between the EIU and control groups.RESULTS：Unique lipid species encompassing all five phospholipid classes were found in both control and the EIU AH and retina.Commensurate with the significantly increased level of lysophospholipids in the EIU AH and retina,we found that the ratio of lysophospholipids to total phospholipids was significantly increased too.We also detected a significant increase in 18：0 lysophosphatidylcholine levels in the EIU group（fold change =6.4 in AH and 3.8 in retina）.Cer240,Cer241,and SM240 levels remarkably increased in the EIU AH.Enhanced C12 ceramide-1-phosphate（C12 C-1-P）,C16 C-1-P,C24 C-1-P,and upregulated Cer160,Cer240,SM120,and SM240 were found in EIU retina.C-1-P was believed to restore homeostasis by inhibiting nuclear factor kappa B（NF-κB） activation.However,we still found elevated NF-κB levels in the EIU retina.CONCLUSION：A variety of lipids might have played a critical role in EIU inflammation.Exogenous topical application of these protective lipids or inhibition of these pro-inflammatory lipids may be useful therapeutic strategies for the resolution of EIU.
基金Supported by the National Natural Science Foundation of China (No.81900911)the National Key R&D Program of China (No.2016YFC0904800,No.2019YFC0840607)+1 种基金the National Science and Technology Major Project of China (No.2017ZX09304010)the Interdisciplinary Program of Shanghai Jiao Tong University (No.YG2019QN66)。
文摘AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical coherence tomography angiography(OCTA).METHODS: RDVCI patients and gender-and agematched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density(PFVD) of retinal deep vascular complex(DVC), ICP, and DCP were analyzed, and the percentage of reduction(PR) of PFVD was calculated.RESULTS: Twenty-four eyes in 22 RDVCI patients(20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls(DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%;chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%;chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%;chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%;all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase(P=0.812), but significant difference in chronic phase(P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC(P=0.735) or ICP(P=0.681) was found, but significant difference in the DCP(P=0.041).CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.
基金funded by National Natural Science Foundation of China(81900869,81730026,81802482)National Key R&D Program(2019YFC0840607,2017YFA0105301)+3 种基金Science and Technology Commission of Shanghai Municipality(17411953000,19495800700)Shanghai Sailing Program(19YF1439500)Talent Project of Revitalizing Liaoning(XLYC1807184)Dalian Science&Technology Innovation Fund(2020JJ26SN050)。
文摘In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.
文摘AIM:To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane(ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis(MF).METHODS:A 23-gauge 3-port pars plana vitrectomy was performed on 16 patients with high MF.A parallel arc line along the vascular arcades was scraped out with a curved membrane scraper DSP.Next,an ILM forceps was used to catch hold of the incisal edge of the ILM flap,and the action of releasing and separating was subsequently taken toward the direction of the macular fovea.Next,the ILM forceps was used to grasp the released area,and the whole area coherent ILM peeling covering the macular fovea was implemented thereafter.Finally,the ILM was folded backwards and peeled off in the arc direction.RESULTS:At the final visit,the average central macular thickness decreased remarkably from 423.76±177.67 to 178.24±66.21 μm.The mean logarithm of the minimum angle of resolution best-corrected visual acuity of 1.37±0.59 was significantly alleviated to 0.74±0.59.CONCLUSION:The wide range of whole piece consecutive ILM peeling without preservation of the epifovea is proven to be effective and significantly reduced the occurrence of retinal tear and macular hole.
基金Supported by the National Key Research and Development Program of China(No.2016YFC0904800)National Natural Science Foundation of China(No.82101181)+1 种基金China Scholarship Council(No.201506230096)Shanghai Sailing Program(No.19YF1439700).
文摘●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
