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

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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Multimodal Nature of the Single-cell Primate Brain Atlas:Morphology,Transcriptome,Electrophysiology,and Connectivity

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Neuroscience Bulletin 2024年第4期40卷 517-532页

作者： Yuhui Shen Mingting Shao Zhao-Zhe Hao Mengyao Huang Nana Xu Sheng Liu State key laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou510060China Guangdong Province key laboratory of Brain Function and Disease Guangzhou510080China

Primates exhibit complex brain structures that augment cognitive *** neocortex fulfills high-cognitive functions through billions of connected *** neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles *** features endow the primate brain atlas with a multimodal *** recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local ***,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

关键词： Neuron Brain atlas Patch-seq Connectivity Primate

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The roles of macrophage migration inhibitory factor in retinal diseases

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Neural Regeneration Research 2024年第2期19卷 309-315页

作者： Hongbing Zhang Xianjiao Zhang Hongsong Li Bing Wang Pei Chen Jiamin Meng shaanxi Institute of ophthalmology Xi’anShaanxi ProvinceChina Department of ophthalmology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina Department of Pathology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive *** are some evidences that MIF is involved in many vitreoretinal *** example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis *** also alleviates trauma-induced and glaucoma-induced optic nerve ***,MIF is critical for retinal/choroidal neovascularization,especially complex *** exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal *** protects uveal melanoma from attacks by natural killer *** mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt *** also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling *** review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

关键词： diabetic retinopathy glaucoma macrophage migration inhibitory factor migration inhibitory factor receptor optic neuropathy retinal degeneration retinal neovascular uveal melanoma uveitis

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Bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium

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International Journal of ophthalmology(English edition) 2024年第4期17卷 646-652页

作者： Xuan Liu Ming Liu Meng Ji Bo Ma Yu-Cen Hou Xin-Yue Yao Qiao-Chu Cheng Li Chen Department of ophthalmology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of ophthalmology Xi’an No.1 HospitalXi’an 710000Shaanxi ProvinceChina shaanxi Institute of ophthalmology Xi’an 710000Shaanxi ProvinceChina Department of ophthalmology Ankang Hospital of Traditional Chinese MedicineAnkang 725000Shaanxi ProvinceChina

AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)*** cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell *** EMT-related indexes and BMP-6 protein levels were detected by Western ***,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression *** EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were ***:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly ***-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in ***,the migration of RPE cells in the BMP-6 siRNA group was also significantly ***-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

关键词： bone morphogenetic protein-6 epithelialmesenchymal transition transforming growth factor-β_(2) retinal pigment epithelial cells cell migration

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Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice

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International Journal of ophthalmology(English edition) 2024年第1期17卷 34-41页

作者： Tong Wang Hai-Chun Li Jin Ma Xi-Ling Yu State key laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina

AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic ***:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic *** 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western *** neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and *** mechanisms underlying the effects of MSC-Shh was ***:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to *** downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to *** extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to ***-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh ***:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic *** ERK1/2,AKT and PI3K pathways are involved in this ***-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

关键词： mesenchymal stem cells Sonic hedgehog signaling reactive gliosis diabetic retinopathy retinal ganglion cells

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Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens

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International Journal of ophthalmology(English edition) 2024年第2期17卷 392-396页

作者： Jun Li Chong-Lin Chen Jia-Qing Li Xiao-Ling Liang Chun Zhang State key laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina

AIM:To investigate the clinical characteristics,treatment methods and outcomes of rhegmatogenous retinal detachment(RRD)in highly myopic eyes with implantable collamer lens(ICL).METHODS:High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were *** ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each ***:A total of nine RRD eyes from nine patients who received V4c-ICL implantation were *** mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo(range,1-60mo).At the initial visit for RRD,giant retinal tear(GRT),horseshoe tear,simple round hole,and horseshoe tear combined with round hole were detected in 3,3,2,and 1 eye(s),respectively,with maculaoff in *** patients received surgical treatment,and one patient was treated by retinal laser photocoagulation *** ICL was preserved in 7 *** the last followup,the mean best corrected visual acuity(BCVA)improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR(P=0.035),and no case of recurrent retinal detachment was ***:The morphological presentation of retinal breaks is diverse in this *** ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data,companied with acceptable visual and anatomical outcomes.

关键词： high myopia implantable collamer lens rhegmatogenous retinal detachment

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Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events:a narrative review

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International Journal of ophthalmology(English edition) 2024年第3期17卷 583-595页

作者： Chun-Li Chen Yi-Zhe Cheng Zhi-Han Zhang Ge Wang Xiao-Yan Peng Department of ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Beijing ophthalmology and Visual Science key laboratory Beijing 100730China State key laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510600Guangdong ProvinceChina

●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field *** previous studies have explained the possible pathogenesis and clinical features of primary ***,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special *** associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular *** related retinal injury is laser photocoagulation,surgery,and *** primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and ***,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with *** possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s *** MEWDS-related features in secondary MEWDS are still evanescent under most *** prognosis and treatment depend on the severity of *** studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal *** pathogenic studies should be conducted in the *** diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

关键词： multiple evanescent white dot syndrome punctate inner choroidopathy multifocal choroiditis secondary multiple evanescent white dot syndrome

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Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis

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International Journal of ophthalmology(English edition) 2024年第1期17卷 66-72页

作者： Yan-Qiao Huang Qian-Zhong Cao Yi-Yao Wang Yi-Jing Zhou Dan-Ying Zheng State key laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To evaluate the effect of lens surgery on health-related quality of life(HRQoL)of preschool children with congenital ectopia lentis(CEL).METHODS:A prospective self-controlled study was conducted in Zhongshan Ophthalmic *** aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this *** of them completed the child and proxy(parental)PedsQL™4.0 before and after the *** preoperative scores were compared to their postoperative *** analyses were performed based on gender and preoperative bilateral presenting visual acuity of the ***:Thirty-two children with CEL successfully underwent surgery without any complications,among whom 8 had monocular surgery and 24 had binocular *** and postoperative questionnaires were completed by 32 child-parent *** intervention could significantly improve the vision of affected children(P<0.001).The medians of physical,psychosocial and total health scores self-reported by the children were 68.75(62.50,81.25),65.00(60.00,80.00)and 67.39(60.87,78.26)preoperatively and were 93.75(87.50,100.00),90.00(83.33,96.67)and 89.13(85.32,95.65)*** preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children(P<0.001).All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents(P<0.001).In the physical functioning evaluation,the preoperative score reported by parents of girls was higher than parents of boys(P=0.041),and the postoperative score of girls was higher than that of boys(P=0.036).CONCLUSION:CEL is associated with significantly worse quality of life in preschool *** intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

关键词： congenital ectopia lentis surgical intervention health-related quality of life preschool children

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Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment

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International Journal of ophthalmology(English edition) 2024年第1期17卷 157-163页

作者： Jia-En Liang Meng-Yin Liang En-En Zhang Yu-Ying Peng Ling-Ling Chen Jia-Yu Deng Ting Lin Jun Fu Jia-Ni Zhang Shao-Li Li Fei Li Hui-Ming Xaio Wen-Min Huang Yu-Hong Liu State key laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical ***:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,*** survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical ***:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical *** characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical *** the exception of age,these characteristics were significantly linked to a higher *** primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key ***:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic *** in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment ***,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.

关键词： participation willingness recruitment strategy ophthalmic clinical trial

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