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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

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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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The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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Neural Regeneration Research 2025年第10期20卷 2741-2757页

作者： Qianzi Jin Suyu Wang Yujia Yao Qin Jiang Keran Li Department of Ophthalmology The Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina The Fourth School of Clinical Medicine Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts ***,the specific pathogenesis remains unclear,and effective early treatment options are consequently *** microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a *** intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other *** dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many *** recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the ***,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s ***,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular ***,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable *** such,the intestinal flora may play an important role in age-related macular *** the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic ***,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular ***-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the inte

关键词： age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora metabolite microecology neurodegenerative disease

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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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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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Toric intraocular collamer lens with anterior chamber maintainer for myopic astigmatism following penetrating keratoplasty:a case report

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International Journal of Ophthalmology(English edition) 2021年第2期14卷 330-332页

作者： Zong-Ming Zhuang Hao-Yu Li Shao-Jian Tan Department of Ophthalmology the First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina jingliang eye hospital of guangxi medical university Nanning 530021Guangxi Zhuang Autonomous RegionChina

Dear Editor,I am Zong-Ming Zhuang,from the Department of Ophthalmology,the First Affiliated hospital of guangxi medical university,Nanning,China.I am writing to present a case of toric intraocular collamer lens(TICL)implantation for myopic astigmatism after penetrating keratoplasty(PK)with anterior chamber maintainer(ACM)and without ophthalmic viscoelastic surgical device(OVD).The current study was conducted in accordance with the Declaration of Helsinki principles,the patient signed a written informed consent.

关键词： maintain implantation intraocular

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Clinical observation of white eye distribution in patients with hyperlipidemia: an artificial intelligence digital visual examination technique

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Journal of Traditional Chinese Medicine 2025年

作者： SONG Tianli LI Haixia LIU Li'an Department of Cardiology， the Guang'anmen hospital， China Academy of Chinese medical Sciences National College， Beijing university of Chinese Medicine

Objective: To explore the clinical observation of white eye distribution characteristics of hyperlipidemic patients based on artificial intelligence digital eye diagnosis technology. Methods: One hundred and fifty subjects were examined in the outpatient and inpatient departments of Guang'anmen hospital of the China Academy of Traditional Chinese Medicine from 01 February 2022 to 01 February 2023， including 80 cases in the hyperlipidemic patient (HLP) group and 70 cases in the normal lipid level patient (NC) group. The two groups were collected and extracted by the artificial intelligence visual diagnostic instrument and analyzed by the MyeyeD-10 white eye shadowless imaging health intelligence analysis system. Finally， SPSS 26.0 (Version X; IBM Corp.， Armonk， NY， USA) was used for statistical processing. Results: Significant differences were noted in the scores of "spot" and "foggy" features between the two groups. Between groups， the "spot" feature score of the white eye morphology in the HLP group (11.07 ± 3.22) was higher than that in the NC group (7.50 ± 4.11) (P eye morphology in the HLP group (8.37 ± 2.25) was higher than that in the NC group (P eye-contact region scores between the two groups， and the "B"， "O" (spleen) and "M" (liver) eye-contact region scores were significantly different. The scores of the white eye channel region in the HLP group were significantly higher than those in the control group， with the "A"， "B"， and "O" regions (P eye choroid in the HLP group were significantly higher than those in the HLP g

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Ocular Trauma in a Rural Population of North China:The Handan eye Study

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Biomedical and Environmental Sciences 2015年第7期28卷 495-501页

作者： ZHOU Jun WANG Feng Hua LU Hai LIANG Yuan Bo WANG Ning Li the Handan eye Study Group Beijing Tongren eye Center Capital Medical University Handan eye hospital School of Optometry and Ophthalmology Eye Hospital Wenzhou Medical University

Objective To determine the prevalence of ocular trauma and the proportion of blindness and visua impairment due to trauma in a rural population in northern China. Methods The Handan eye Study is a population-based cross-sectional study that surveyed 6830 Chinese people aged 30＋ years from 13 randomly selected villages in Yongnian County, city of Handan, Hebei Province, in July, 2006. All participants underwent a standardized interview and extensive examinations. A structured questionnaire was used to collect information on ocular trauma. Results Of the 5837 participants who filled out the questionnaire, 124 subjects [2.1%; 95% confidence interval （CI）, 1.8%-2.5%] reported a history of ocular trauma in either eye, including 19 （0.3%） persons reporting trauma in both eyes. Men were more likely to have an eye injury than women [odds ratio （OR）, 3.3; 2.2-4.9]. In multiple logistic regression models, ocular trauma was significantly more frequent among normotensive participants when compared with hypertensive participants （hypertensive vs. normotensive＂ OR, 0.6; 0.4-0.9） and among participants who had a history of falls （OR, 2.4; 1.2-4.8）. The proportion of unilateral visual impairment and unilateral blindness due to trauma were 10.5% （13 subjects） and 21.0% （26 subjects）, respectively. Conclusion Our study reports the prevalence of severe ocular trauma among adults in rural China, revealing a high proportion of blindness and visual impairment due to trauma. These findings suggest the need for educational strategies to increase eye health awareness in this rural population with focus on providing at least appropriate first aid care to reduce blindness due to trauma.

关键词： Ocular trauma Population-based survey Prevalence Risk factor Handan eye Study

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Optical coherence tomography with or without enhanced depth imaging for peripapillary retinal nerve fiber layer and choroidal thickness

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International Journal of Ophthalmology(English edition) 2017年第10期10卷 1539-1544页

作者： Meng-Ai Wu Wei-Xin Xu Zhe Lyu Li-Jun Shen eye hospital of Wenzhou medical university

AIM：To assess peripapillary retinal nerve fiber layer（RNFL）and choroidal thickness obtained with enhanced depth imaging（EDI）mode compared with those obtained without EDI mode using Heidelberg Spectralis optical coherence tomography（OCT）.METHODS：Fifty eyes of 25 normal healthy subjects and32 eyes of 20 patients with different eye diseases were included in the *** subjects underwent 3.4 mm diameter peripapillary circular OCT scan centered on the optic disc using both the conventional and the EDI OCT *** visualization of RNFL and choroidoscleral junction was assessed using an ordinal scoring *** paired t-test,intraclass correlation coefficient（ICC）,95%limits of agreement（LoA）,and Bland and Altman plots were used to test the agreement of ***：The visibility score of RNFL obtained with and without EDI was of no significant difference（P=0.532）,the visualization of choroidoscleral junction was better using EDI protocol than conventional protocol（P〈0.001）.Peripapillary RNFL thickness obtained with EDI was slightly thicker than that obtained without EDI（103.25±9.42μm vs 101.87±8.78μm,P=0.010）.The ICC of the two protocols was excellent with the value of 0.867 to 0.924,the 95%LoA of global RNFL thickness was between-10.0 to 7.4μ*** choroidal thickness obtained with EDI was slightly thinner than that obtained without EDI（147.23±51.04μm vs 150.90±51.84μm,P〈0.001）.The ICC was also excellent with the value of 0.960 to 0.987,the 95%LoA of global choroidal thickness was between-12.5 to 19.8μ***：Peripapillary circular OCT scan with or without EDI mode shows comparable results in the measurement of peripapillary RNFL and choroidal thickness.

关键词： enhanced depth imaging optical coherence tomography choroidal thickness peripapillary retinal nerve fiber layer

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Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

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International Journal of Ophthalmology(English edition) 2015年第4期8卷 659-664页

作者： Li-Fei Yuan Guang-Da Li Xin-Jun Ren Hong Nian Xiao-Rong Li Xiao-Min Zhang Tianjin medical university eye hospital & eye Institute Hebei eye hospital Linyi People's hospital

· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in *** also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in *** is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

关键词： experimental autoimmune uveoretinitis rapamycin regulatory T cells Th1 cells Th2 cells Th17 cells uveitis

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