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Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

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International Journal of ophthalmology(English edition) 2024年第4期17卷 676-685页

作者： Ting-Ting Feng Xiang Gao An-Ran Liang Bo-Wen Zhao Guang-Hui He Song Chen clinical College of ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of ophthalmology and Visual Science Tianjin Eye InstituteTianjin Eye HospitalTianjin 300020China Key Laboratory of ophthalmology Anyang Eye HospitalAnyang 455000Henan ProvinceChina Department of ophthalmology Jining No.1 People’s HospitalJining 272011Shandong ProvinceChina

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of ***:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free *** differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were ***:A total of 12 samples were *** proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were *** found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept *** functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by *** addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural *** addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in ***:Proteomic analysis is an approach of choice to explore the molecular mechanisms of *** data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

关键词： vitreous proliferative diabetic retinopathy proteome 4D label-free

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Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses

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International Journal of ophthalmology(English edition) 2024年第5期17卷 822-830页

作者： Fang Ruan Wen-Jun Kong Qian Fan Hong-Wei Dong Wei Zhang Wen-Bin Wei Ying Jie Department of ophthalmology Beijing You’an HospitalCapital Medical UniversityBeijing Infectious Eye Disease Diagnosis and Treatment CenterBeijing 100069China Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijing Institute of OphthalmologyBeijing Ophthalmology and Visual Sciences Key LabBeijing 100730China Tianjin Eye Hospital Tianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteNankai University Affiliated Eye HospitalNankai University Eye InstituteNankai UniversityClinical College of OphthalmologyTianjin Medical UniversityTianjin 300020China

AIM:To evaluate dry eye disease(DED)symptomatology and mental health status in different COVID-19 ***:A cross-sectional observational design was *** 123 eligible adults(46.34%of men,age range,18-59y)with COVID-19 included in the study from August to November,*** Surface Disease Index(OSDI),Five-item Dry Eye Questionnaire(DEQ-5),Hospital Anxiety and Depression Scale(HADS),and Pittsburgh Sleep Quality Index(PSQI)were used in this ***:OSDI scores were 6.82(1.25,15.91)in asymptomatic carriers,7.35(2.50,18.38)in mild cases,and 16.67(4.43,28.04)in recurrent cases,with 30.00%,35.56%,and 57.89%,respectively evaluated as having DED symptoms(χ2=7.049,P=0.029).DEQ-5 score varied from 2.00(0,6.00)in asymptomatic carriers,3.00(0,8.00)in mild cases,and 8.00(5.00,10.00)in recurrent cases,with 27.50%,33.33%,and 55.26%,respectively assessed as having DED symptoms(χ2=8.532,P=0.014).The prevalence of clinical anxiety(50.00%)and depression(47.37%)symptoms were also significantly higher in patients with recurrent infection(χ2=24.541,P<0.001;χ2=30.871,P<0.001).Recurrent infection was a risk factor for high OSDI scores[odds ratio,2.562;95%confidence interval(CI),1.631-7.979;P=0.033]and DEQ-5 scores(odds ratio,3.353;95%CI,1.038-8.834;P=0.043),whereas having a fixed occupation was a protective factor for OSDI scores(odds ratio,0.088;95%CI,0.022-0.360;P=0.001)and DEQ-5 scores(odds ratio,0.126;95%CI,0.039-0.405;P=0.001).CONCLUSION:Patients with recurrent COVID-19 have more severe symptoms of DED,anxiety,and depression.

关键词： COVID-19 dry eye disease recurrent infection mental health

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Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

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International Journal of ophthalmology(English edition) 2024年第5期17卷 806-814页

作者： Si-Rui Zhou Yu-Sheng Zhu Wen-Ting Yuan Xiao-Yan Pan Tong Wang Xiao-Dong Chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi institute of ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell ***:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in *** viability was detected by a Cell Counting Kit-8 *** proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,*** expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot *** MET and phosphorylated MET proteins were also determined by immunofluorescence ***:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT ***11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT ***11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 ***,SU11274 also blocked HGF-induced phosphorylation of MET and AKT ***:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor ***-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

关键词： hepatocyte growth factor mesenchymal epithelial transition factor SU11274 retinal pigment epithelial cells

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Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

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International Journal of ophthalmology(English edition) 2024年第6期17卷 1018-1027页

作者： Yu-Sheng Zhu Si-Rui Zhou Hui-Hui Zhang Tong Wang Xiao-Dong Chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi institute of ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)***:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL *** and EGFR siRNA were used to intervene EGF *** viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,***/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot *** was also determined by immunofluorescence ***:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR *** suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein *** also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin ***,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin ***:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE *** inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

关键词： erlotinib epidermal growth factor receptor protein kinase B epithelial-mesenchymal transition retinal pigment epithelium cell

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Inhibition of viability of human retinal microvascular endothelial cells by vialinin A under high glucose condition

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International Journal of ophthalmology(English edition) 2024年第10期17卷 1809-1815页

作者： Zhi-Gang Chen Gao-Qin Liu Wei-Ming Liu Pei-Rong Lu Department of ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Jiangsu clinical Immunology institute the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

AIM:To investigate the effects of vialinin A on viability of human retinal endothelial cells(HRECs)under high glucose condition and its potential ***:The HRECs were divided into four groups:normal glucose control group(NG,5 mmol/L D-glucose),high glucose group(HG,30 mmol/L D-glucose),HG+1μmol/L vialinin A group,and HG+5μmol/L vialinin A *** cell viabilities were measured with cell counting kit-8(CCK-8)assay for proliferation,with scratch assay for migration,and tube formation,for evaluation of the impact of vialinin A on cellular ***-time PCR and Western blotting were used to determine the expression level of vascular endothelial growth factor(VEGF).RESULTS:The proliferative capacity and migration of HRECs was reduced by 5μmol/L vialinin A in high glucose environment(both P<0.05).Vialinin A also inhibited highglucose-induced tube formation of *** expression level of VEGF and PI3K in HRECs was also significantly decreased by vialinin A(P<0.05).CONCLUSION:Vialinin A inhibits the cell viability of *** may serve as a potential target for anti-angiogenic therapy.

关键词： vialinin A vascular endothelial growth factor human retinal endothelial cells cell viability

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OCTA characteristics in non-arteritic central retinal artery occlusion and correlation with visual acuity

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International Journal of ophthalmology(English edition) 2024年第2期17卷 289-296页

作者： Hong-Xia Gong Bin Wu Shi-Yong Xie Wei Zhang Song Chen Tianjin Key Lab of ophthalmology and Visual Science Department of Ophthalmology for Integrated Traditional Chinese and Western MedicineTianjin Eye HospitalTianjin 300020China clinical College of ophthalmology Tianjin Medical UniversityTianjin 300010China Eye Hospital Affiliated to Nankai University Tianjin 300020China

AIM:To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion(NA-CRAO)via optical coherence tomography angiography(OCTA)and analyze their correlation with visual ***:Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into:A type(mild n=29),B type(moderate n=27)and C type(severe n=6)based on the degree of visual loss,retinal edema,and arterial blood flow delay in fundus fluorescence angiography(FFA).Contralateral healthy eyes were used as the control ***-corrected visual acuity(BCVA),slit lamp microscopy,indirect ophthalmoscopy,fundus color photography,OCTA,and FFA were ***’s correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual ***:There were no statistically significant differences in age,gender,and intraocular pressure among the three types and the control group(P>0.05).Vessel density in deep capillary plexus(VD-DCP)significantly decreased(P<0.05)in all three types of NA-CRAO patients compared to the control *** density in superficial vascular plexus(VD-SVP)significantly decreased(P<0.05)in type A patients and choriocapillaris flow area significantly decreased(P<0.05)in type B and type C patients compared to the control group;while outer retinal flow areas significantly increased in the type A(P<0.05)and decreased in type C patients(P<0.05).The retinal thickness significantly increased in type C group(P<0.05).The VD-SVP at fovea in the type A was significantly lower than both of type B and *** VD-SVP at nasal parafovea in type A and B was significantly lower than type C(P<0.05).The logMAR BCVA of type A was significantly better than that of type B and C groups(P<0.05).Spearman’s correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea(r=0.679,P=0.031)and nasal parafovea(r=0.826,P=0.013).CONCLUSION:OCTA is valua

关键词： non-arteritic central retinal artery occlusion fundus fluorescence angiography optical coherence tomography angiography retinal vessel density visual acuity

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Turning point of organoid transplantation:first-in-human trial of iPSC-derived retinal organoid grafting in patients with retinitis pigmentosa

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Science China(Life Sciences) 2024年第5期67卷 1082-1084页

作者： Chang-Jun Zhang Zi-Bing Jin Beijing institute of ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China

The discovery of induced pluripotent stem cells(iPSCs)has revolutionized the field of disease research,providing a promising platform for studying various *** the last decade,significant progress has been made in combining iPSCs with other cutting-edge technologies to investigate disease mechanisms and develop potential treatments.

关键词： conditions patients retinitis

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Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2024年第11期19卷 2543-2552页

作者： Sam Enayati Karen Chang Anton Lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen Schepens Eye Research institute of Massachusetts Eye and Ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA institute of clinical medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Biochemistry Oslo University HospitalUniversity of OsloOsloNorway Department of ophthalmology Drammen HospitalVestre Viken Hospital TrustDrammenNorway Department of Histology and Embryology School of MedicineMarmara UniversityIstanbulTurkiye

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor *** research supports the beneficial effect of electrical stimulation on photoreceptor *** study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal ***,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem *** this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp *** investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with *** retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in *** density was evaluated by rhodopsin *** vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp *** function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),*** was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse *** recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest *** of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human *** tem

关键词： bipolar cells electrical stimulation neuroprotection photoreceptor degeneration retina retinal explants retinitis pigmentosa transcorneal electrical stimulation waveform

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Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions

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International Journal of ophthalmology(English edition) 2024年第8期17卷 1403-1410页

作者： Yue Zhang Xiao-Jing Liu Xin-Ran Zhai Yao Yao Bin Shao Yu-Han Zhen Xin Zhang Zhe Xiao Li-Fang Wang Ming-Lian Zhang Zhi-Min Chen Hebei Eye Hospital Provincial Key Laboratory of OphthalmologyHebei Provincial Clinical Research Center for Eye DiseasesXingtai 054001Hebei ProvinceChina Department of ophthalmology Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic ***:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and *** the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR *** lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in *** glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in *** vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,***:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq ***,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA *** of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction *** vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose ***-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in ***:The expression level of FBN1 increases in reti

关键词： diabetic retinopathy fibrillin-1 retinablood barrier vascular leakage vascular permeability apoptosis retinal vascular endothelial cells

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Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling

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Journal of Biomedical Research 2024年第3期38卷 256-268页

作者： Huan Li Huiying Zhang Lushu Chen Yaming Shen Yuan Cao Xiumiao Li Jin Yao Department of ophthalmology the Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of ophthalmology the Fourth School of Clinical MedicineNanjing Medical UniversityNanjingJiangsu 210029China

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,*** current clinical treatment is not very *** investigated indirubin,one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill,in the present study for its role in retinal *** exhibited no detectable tissue toxicity in vivo or cytotoxicity in ***,indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in ***,indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in *** addition,indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative ***,indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 *** conclusion,indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush *** present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

关键词： retinal neurodegenerative disease oxidative stress PI3K/AKT retinal ganglion cell apoptosis

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