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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina national Clinical Research center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei Henan eye hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of national Clinical Research center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang Department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina national Clinical Research center for eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

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Revealing and predicting the long-term biomechanical response of orthokeratology by developing a patient-specific computational model

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 156-168页

作者： Yifeng Li Zhuoran Yang Ziming Yan Huibin Shi Zhanli Liu Kaijie Wang Department of Engineering Mechanics School of Aerospace Engineering Tsinghua University Beijing Tongren eye center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Lab

Orthokeratology(OK) is widely used for effective myopia correction and control. However, the incomplete understanding of its biomechanical mechanisms makes OK lens fitting rely heavily on clinician judgment, complicating accurate predictions of treatment outcomes. In this paper, we performed clinical experiments and numerical analysis to study corneal deformation modes and long-term changes in central corneal thickness. Clinical experiments were conducted on 194 Chinese myopic patients under OK treatment for 3 months. Based on the experimental data, a patient-specific computational biomechanical model for OK was established and validated. Specifically, the anisotropic mechanical properties of the cornea were incorporated into the model to describe the significant difference between its shear modulus(29.5 kPa) and tensile modulus(768.4 kPa). Additionally, a viscohyperelastic material model with a prolonged corneal relaxation time of 5.6 h was developed to capture the long-term deformation response. The results show that corneal thickness reduction in OK is primarily due to out-of-plane shear deformation,influenced by the cornea's low shear resistance. Modeling the extended corneal relaxation time is crucial for predicting long-term biomechanical responses. The computational model effectively captures long-term changes in central corneal thickness, potentially improving OK lens fitting accuracy.

关键词： orthokeratology computational biomechanical model long-term viscoelasticity myopia correction

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Vision rehabilitation using microperimetric biofeedback training in age-related macular degeneration

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International Journal of Ophthalmology(English edition) 2023年第6期16卷 933-938页

作者： Sri Hudaya Widihastha Erwin Iskandar Karmelita Satari Irawati Irfani Rova Virgana Primawita Oktarima Amiruddin Department of Ophthalmology Faculty of MedicineUniversitas PadjadjaranBandung 40117Indonesia national eye center cicendo hospital Bandung 40117Indonesia

·AIM: To determine the impact of microperimetric biofeedback training(MBFT) on the quality of vision in patients with age-related macular degeneration(AMD).·METHODS: This study was a prospective, interventional, comparative study with subjects of patients diagnosed with AMD in the national eye center cicendo eye hospital, Indonesia. Patients were randomly divided into two groups, intervention and non-intervention with 18 patients in each group. The intervention group would receive six MBFT training sessions of 10-minute time duration each.·RESULTS: A statistically significant improvement of best corrected visual acuity(BCVA) was found after the intervention, from 1.24±0.416 to 0.83±0.242(log MAR;P<0.001). A statistically significant improvement for near vision acuity(NVA) was also observed, from 1.02±0.307 log MAR to 0.69±0.278 log MAR(P<0.001). In addition, reading rate increased, from 40.83±30.411 to 65.06±31.598 words/min(P<0.001). Similarly, a comparison of changes in BCVA, NVA, and reading rate between intervention and non-intervention groups showed a significant difference(P<0.001).·CONCLUSION: MBFT significantly and positively impacts visual acuity, NVA, and reading rate in patients with AMD.

关键词： microperimetric biofeedback training agerelated macular degeneration vision rehabilitation

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Comparison of the Refraction Precision Results between Pentacam AXL and IOL Master 700 Using Universal II Barrett Formula after Cataract Surgery

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Open Journal of Ophthalmology 2023年第1期13卷 1-12页

作者： Budiman Tjokrovonco Ludwig Melino Sugiarti Emmy Dwi Knoch Andrew Maximilian Cataract and Refractive Surgery Unit Cicendo National Eye Center Bandung Bandung Indonesia Department of Ophthalmology Faculty of Medicine Universitas Padjajaran/National Eye Center - Cicendo Eye Hospital Bandung Indonesia

Background: The availability of premium intraocular lenses (IOL), including toric, multifocal, and EDOF, has become very sophisticated and now demands accurate biometric measurement accuracy. The Pentacam AXL and IOL Master 700 are often used for optical biometry and they are available in the market today. They can also be used to measure the parameters needed in the IOL calculation using the latest generation formulas, such as the Barett Universal II. Therefore, this study aims to compare the accuracy of refraction results between Pentacam AXL compared to IOL Master 700 after cataract surgery with the Barett Universal-II formula. Method: A total of 64 eyes from 64 patients who had a preoperative examination with IOL Master 700 and Pentacam AXL were included in this study. Parameters such as K, ACD, LT, WTW, and AL were then compared between the two tools. Prediction error values were also calculated and compared based on the difference between the Spherical equivalent (SE) of subjective refraction results after 4 weeks of surgery with their refractive prediction targets. Results: There was no statistically significant difference in the parameters measured from the two tools except ACD and WTW. Furthermore, LT was difficult to obtain on the Pentacam AXL due to penetration problems, as well as in patients with significant lens opacities. The percentage of error prediction values that reach ± 0.50 D on Pentacam AXL and IOL Master 700 was 70.3% and 73.5%, respectively. However, the average prediction error that was close to emmetropia with IOL Master 700 was greater compared to the other tool. Conclusion: Pentacam AXL has a fairly good accuracy for refraction prediction compared to IOL Master 700. However, it is still necessary to optimize its constants to obtain optimal results.

关键词： Error Prediction Biometry IOL Master 700 Pentacam AXL

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Pediatric Retinal Detachment in Indonesia: Clinical Characteristics, Risk Factors, and Treatment Outcomes

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Open Journal of Ophthalmology 2017年第4期7卷 249-255页

作者： Irawati Irfani Arief S. Kartasasmita Universitas Padjadjaran/cicendo national eye hospital Bandung Indonesia

Purpose: To describe the clinical features and risk factors of pediatric retinal detachment among patients in Indonesia. Methods: This is a retrospective study involving 46 eyes of 34 children (younger than 18 years) diagnosed with pediatric retinal detachment. A detailed history was taken and a complete ophthalmic examination and a systemic examination were performed as required. Clinical characteristics, risk factors, and treatment choices were noted. Retinal detachment was categorized as tractional, exudative, or rhegmatogenous. Results: Mean patient age was 8.5 years (range, 0–18 years). Most patients (70%) were boys. Twelve (35%) patients had bilateral involvement at presentation. Tractional retinal detachment was found in 17 eyes (37%) and in this study was caused by retinopathy of prematurity (grade IV-V) in all cases. Exudative retinal detachment was found in 12 eyes (26%), the most common causes of which were panuveitis and Coat’s disease (both 50%). Rhegmatogenous retinal detachment was found in 17 eyes (37%), the most common risk factor for which was trauma (58%). Conclusions: Different approaches are needed to treat pediatric retina detachment in patients with different risk factors. Recognition of risk factors and early management will help to prevent childhood blindness due to retinal detachment.

关键词： Pediatric Retinal Detachment Clinical Characteristics Risk Factors

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Factors affecting visual outcome of myopic choroidal neovascularization treated with verteporfin photodynamic therapy

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International Journal of Ophthalmology(English edition) 2013年第3期6卷 327-330页

作者： Colin S. Tan Milton C. Chew Kai-Hung Lim Tock-Han Lim national Healthcare Group eye Institute Tan Tock Seng Hospital Fundus Image Reading center National Healthcare Group Eye Institute

AIM: To evaluate the visual outcomes of choroidal neovascularization (CNV) secondary to pathological myopia and the impact of novel risk factors affecting the final visual outcome. ·METHODS: Interventional case series of 18 consecutive patients with pathological myopia treated with photodynamic therapy (PDT). Inclusion criteria were spherical equivalent -6D or worse or features of pathological myopia on retinal examination. The main outcome measure was final best -corrected visual acuity (BCVA). ·RESULTS: Of 18 eyes, 13 (72.2%) avoided moderate visual loss (≥3 lines of LogMAR BCVA) and 5 eyes (27.8%) improved by at least 1 line after 1 year. Patients with LogMAR BCVA ≤0.3 (Snellen equivalent 20/40) at one year were younger than those with BCVA >0.3 (mean age 39.0 vs 61.6 years, P =0.001). A higher proportion of eyes with greatest linear dimension (GLD) of ≤1 000μm avoided moderate visual loss (100% vs 50%, P =0.026). Among patients who were treated within 2 weeks of visual symptoms, 88.9% avoided the loss of 3 or more lines compared to 55.6% for those who presented later. The mean improvement in LogMAR BCVA of those with GLD ≤1 000μm was +0.12 compared to a loss of 0.55 LogMAR units for those with GLD >1 000μm (P =0.02). Visual outcomes were not associated with gender or refractive error.·CONCLUSION: Good visual outcome in myopic CNV is associated with younger age, smaller lesion size and earlier initiation of treatment. These factors are relevant for ophthalmologists considering treatment options for myopic CNV.

关键词： myopic choroidal neovascularization pathologic myopia photodynamic therapy

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Review on current concepts of myopia and its control strategies

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International Journal of Ophthalmology(English edition) 2021年第4期14卷 606-615页

作者： Raju Kaiti Ranjila Shyangbo Indra Prasad Sharma Manish Dahal Nepal eye hospital Kathmandu 44600Nepal national Academy of Medical Sciences Kathmandu 44600Nepal Gyalyum Kesang Choeden Wangchuck national eye center JDW National Referral HospitalThimpu 11001Bhutan

Myopia poses a significant burden on the healthcare system,economy and quality of *** is an emerging global public health challenge and requires interventions to delay or stop onset and *** changing times and evidence,the concepts of myopia are changing along with the treatment and control *** modifications including increased outdoors time and reduced near work,optical and pharmaceutical management options are *** paper presents a current overview on the concepts of myopia,and is expected to summarize updates on myopia control methods.

关键词： atropine myopia myopia control myopic maculopathy public health

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Inhibition of cell proliferation,migration and apoptosis in blue-light illuminated human retinal pigment epithelium cells by down-regulation of HtrA1

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International Journal of Ophthalmology(English edition) 2017年第4期10卷 524-529页

作者： Tian Yu Chang-Zheng Chen Yi-Qiao Xing eye center Renmin Hospital of Wuhan University

AIM：To investigate the effect of Htr A1 on the proliferation,migration and apoptosis of human retinal pigment epithelium（RPE） cells in the light injured model,as well as the expression of the apoptosis related ***：The human RPE cell line ARPE-19 was exposed to blue light to establish the light injured *** cells were transfected with Htr A1 si RNA to knockdown Htr A1 *** expression of Htr A1 was determined by real-time polymerase chain reaction（RTPCR） and Western blot,*** in cell proliferation,migration and apoptosis were assessed by cell counting kit-8（CCK-8）,Transwell assay and flow cytometry respectively,as well as changes in the m RNA and protein levels of Bax,Caspase-3 and Bcl-2 ***：Htr A1 was highly expressed in ARPE-19 cells after blue light *** of Htr A1 expression inhibited the proliferation,migration and apoptosis of the blue-light-irradiated ARPE-19 cells（P〈0.05）.Bax and Caspase-3 expression were significantly reduced both at m RNA and protein levels（P〈0.05） after si RNA ***-2 expression significantly increased in blue-lightirradiated ARPE-19 cells after si RNA interference（P〈0.05）.CONCLUSION：Silence of Htr A1 may inhibit the proliferation,migration and apoptosis of ARPE-19 cells in light injured ***,Htr A1 suppression in blue-lightirradiated ARPE-19 cells may ameliorate cell apoptosis through down-regulation of Bax and Caspase-3,and upregulation of Bcl-2 expression.

关键词： HtrA1 retinal pigment epithelium small interfering RNA

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