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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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Axial length,vitreoretinal pathology,and anterior chamber depth can predict postoperative refractive outcomes in phacovitrectomy/silicone oil removal

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International Journal of Ophthalmology(English edition) 2023年第4期16卷 554-562页

作者： Xu Chen He Zhao Jia-Yun Ren Lu Wang Jun-Li Wan Bo Liu Nan Wu Xi Liu Yong Liu Southwest Hospital/Southwest Eye Hospital Army Medical UniversityChongqing 400038China key lab of visual damage and regeneration&restoration of chongqing Chongqing 400038China

AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract ***:The study is a retrospective,case-series *** 301 eyes of 301 patients undergoing combined PPV/SOR with cataract surgery were *** individuals were separated into four groups according to their preoperative diagnoses:silicone oil-filled eyes after PPV(group 1),epiretinal membrane(group 2),macular hole(group 3),and primary retinal detachment(RD;group 4).The variables af fecting postoperative refractive outcomes were analyzed,including age,gender,preoperative best-corrected visual acuity(BCVA),axial length(AL),keratometry average,anterior chamber depth(ACD),intraocular tamponade,and vitreoretinal *** outcome measurements include the mean refractive PE and the proportions of eyes with a PE within±0.50 diopter(D)and±1.00 ***:For all patients,the mean PE was-0.04±1.17 D,and 50.17%of patients(eyes)had a PE within±0.50 *** was a significant difference in refractive outcomes among the four groups(P=0.028),with RD(group 4)showing the least favorable refractive *** multivariate regression analysis,only AL,vitreoretinal pathology,and ACD were strongly associated with PE(all P26 mm)and a deeper ACD were correlated with hyperopic PE,and shorter eyes(AL<26 mm)and a shallower ACD were correlated with myopic ***:RD patients have the least favorable refractive ***,vitreoretinal pathology,and ACD are strongly associated with PE in the combined *** three factors affect refractive outcomes and thus can be used to predict a better postoperative refractive outcome in clinical practice.

关键词： axial length vitreoretinal pathology anterior chamber depth intraocular lens pars plana vitrectomy silicone oil removal cataract combined surgery refractive error intraocular tamponade

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Optical control after transfection of channelrhodopsin-2 recombinant adenovirus in visual cortical cells

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Neural regeneration Research 2012年第16期7卷 1228-1233页

作者： Junping Yao Wensheng Hou Hao Wang Hui Liu Chuanhuang Weng Zhengqin Yin College of Bioengineering Chongqing UniversityChongqing 400044China chongqing key lab of visual damage and regeneration&restoration Chongqing 400038China Department of Ophthalmology Southwest HospitalThird Military Medical University of Chinese PLAChongqing 400038China

Channelrhodopsin-2 ectopically expressed in the retina can recover the response to blue light in genetically blind mice and rats, but is unable to restore visual function due to optic nerve or optic tract lesions. Long Evans rats at postnatal day 1 were used for primary culture of visual cortical cells and 24 hours later, cells were transfected with recombinant adenovirus carrying channelrhodopsin-2 and green fluorescent protein genes. After 2 4 days of transfection, green fluorescence was visible in the cultured cells. Cells were stimulated with blue light （470 nm）, and light-induced action potentials were recorded in patch-clamp experiments. Our findings indicate that channelrhodopsin-2-recombinant adenovirus transfection of primary cultured visual cortical cells can control the production of action potentials via blue light stimulation.

关键词： channelrhodopsin-2 recombinant adenovirus visual cortex blue light action potentials neuralregene ration

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Organoid-derived human retinal progenitor cells promote early dedifferentiation of Müller glia in Royal College of Surgeons rats

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International Journal of Ophthalmology(English edition) 2023年第4期16卷 483-498页

作者： Qiang Guo Yu-Xiao Zeng Shu-Dong Huang Ting Zou Zheng-Qin Yin Southwest Hospital/Southwest Eye Hospital Third Military Medical University(Army Medical University)Chongqing 400038China key lab of visual damage and regeneration&restoration of chongqing Chongqing 400038China

AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferentiation,thus improving visual function and delaying retinal degenerative ***:h ERO-RPCs were subretinally transplanted into Royal College of Surgeons(RCS)***(ERG)recording was performed at 4 and 8wk postoperation to assess retinal *** immunofluorescence,the changes in outer nuclear layer(ONL)thickness and retinal Müller glia were explored at 2,4,and 8wk *** verify the effect of h ERO-RPCs on Müller glia in vitro,we cocultured h ERO-RPCs with Müller glia with a Transwell *** coculture,Ki67 staining and quantitative polymerase chain reaction(q PCR)were performed to measure the proliferation and m RNA levels of Müller glia *** migration experiment was used to detect the effect of h ERO-RPCs on Müller glial *** between two groups were performed by the unpaired Student’s t-test,and comparisons among multiple groups were made with one-way ANOVA followed by Tukey’s multiple comparison ***:The visual function and ONL thickness of RCS rats were significantly improved by transplantation of h ERO-RPCs at 4 and 8wk *** addition to inhibiting gliosis at 4 and 8wk postoperation,h ERO-RPCs significantly increased the expression of dedifferentiation-associated transcriptional factor in Müller glia and promoted the migration at 2,4 and 8wk postoperation,but not the transdifferentiation of these cells in RCS *** vitro,using the Transwell system,we found that h ERO-RPCs promoted the proliferation and migration of primary rat Müller glia and induced their dedifferentiation at the m RNA ***:These results show that h ERO-RPCs might promote early dedifferentiation of Müller glia,which may provide novel insights into the mechanisms of stem cell

关键词： retinal degeneration retinal organoid retinal progenitor cells subretinal transplantation Muller glia dedifferentiation

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Pediatric ocular trauma with pars plana vitrectomy in Southwest of China:clinical characteristics and outcomes

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International Journal of Ophthalmology(English edition) 2021年第9期14卷 1321-1326页

作者： Zuo-Xin Qin Yan He Yu-Fei Xu Tao Yu Yong Liu Nan Wu Southwest Hospital/Southwest Eye Hospital Third Military Medical University(Army Medical University)Chongqing 400038China key lab of visual damage and regeneration&restoration of chongqing Chongqing 400038China

AIM:To investigate the clinical characteristics and predictive factors of pediatric ocular trauma patients with ***:Pediatric ocular trauma patients(aged 14 y or younger)who received vitrectomy in Southwest Hospital between January 2007 and December 2017 were reviewed ***,gender,mechanism of injury,final visual acuity(VA),and prognostic factors were ***:A total of 139 eyes in 139 pediatric patients were included in the *** mean age was 7.4±3.7 years old and the male-to-female ratio was 5:*** were 104(74.8%)open globe injuries and 35(25.2%)closed globe *** top one traumatic eye injuries were penetrating injuries occur through sharp metal objects(43.9%).After vitrectomy,116 patients had favorable anatomic outcome at the last follow-up,and 30 eyes(21.6%)achieved VA of 20/200 or *** univariate analysis,we found zone III injuries(P=0.021),poor initial VA(P=0.005),endophthalmitis(P=0.024),and recurrent retinal detachment(Pvisual outcome of severe pediatric ocular trauma.

关键词： pediatric ocular trauma vitrectomy outcome

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International Journal of Ophthalmology(English edition) 2021年第8期14卷 1138-1150页

作者： Hao-Jue Xu Qi-You Li Ting Zou Zheng-Qin Yin Southwest Hospital/Southwest Eye Hospital Third Military Medical University(Army Medical University)Chongqing 400038China key lab of visual damage and regeneration&restoration of chongqing Chongqing 400038China

AIM:To explore the temporal mitochondrial characteristics of retinal pigment epithelium(RPE)cells obtained from human embryonic stem cells(hESC)-derived retinal organoids(hEROs-RPE),to verify the optimal period for using hEROs-RPE as donor cells from the aspect of mitochondria and to optimize RPE cell-based therapeutic strategies for age-related macular degeneration(AMD).METHODS:RPE cells were obtained from hEROs and from spontaneous differentiation(SD-RPE).The mitochondrial characteristics were analyzed every 20 d from day 60 to *** quantity was measured by MitoTracker Green *** electron microscopy(TEM)was adopted to assess the morphological features of the mitochondria,including their distribution,length,and *** membrane potentials(MMPs)were determined by JC-1 staining and evaluated by flow cytometry,reactive oxygen species(ROS)levels were evaluated by flow cytometry,and adenosine triphosphate(ATP)levels were measured by a *** between two groups were analyzed by the independentsamples t-test,and comparisons among multiple groups were made using one-way ANOVA or Kruskal-Wallis H test when equal variance was not ***:hEROs-RPE and SD-RPE cells from day 60 to 160 were successfully differentiated from hESCs and expressed RPE markers(Pax6,MITF,Bestrophin-1,RPE65,Cralbp).RPE features,including a cobblestonelike morphology with tight junctions(ZO-1),pigments and microvilli,were also observed in both hEROs-RPE and SDRPE *** mitochondrial quantities of hEROs-RPE and SD-RPE cells both peaked at day ***,the cristae of hEROs-RPE mitochondria were less mature and abundant than those of SD-RPE mitochondria at day 80,with hEROsRPE mitochondria becoming mature at day *** hEROs-RPE and SD-RPE cells showed low ROS levels from day 100 to 140 and maintained a normal MMP during this ***,hEROs-RPE mitochondria maintained a longer time to produce high levels of ATP(from day 120

关键词： mitochondria retinal organoids retinal pigment epithelium cells human embryonic stem cells,retinal degenerative diseases

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Outcomes and risk factors for failure of trabeculectomy in glaucomatous patients in Southwest China:a 325 eyes analysis

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International Journal of Ophthalmology(English edition) 2023年第3期16卷 367-374页

作者： Zuo-Xin Qin Xi Ying Qing Han Lu Wang Lian Tan Yu-Fei Xu Qiu-Xiang You Nan Wu Yong Liu Southwest Hospital/Southwest Eye Hospital Third Military Medical University(Army Medical University)Chongqing 400038China key lab of visual damage and regeneration&restoration of chongqing Chongqing 400038China

AIM:To evaluate the outcomes and elucidate the failure factors for trabeculectomy with mitomycin C(MMC)in Southwest Chinese ***:A retrospective correlational study was conducted on the glaucomatous patients who underwent initial trabeculectomy with MMC in Southwest Hospital and had been followed up for 1-3y.A complete success for surgery is defined as a postoperative intraocular pressure(IOP)>5 and≤21 mm Hg and 20%reduction of IOP compared to preoperative,without IOP-lowering medications.A qualified success for surgery is defined as the abovementioned postoperative IOP with or without IOP-lowering *** primary outcomes were IOP,the number of IOP-lowering medications,and cumulative success *** secondary outcomes included best corrected visual acuity(BCVA),mean deviation(MD)of visual field,major complications,and risk factors for surgical ***:A total of 325 eyes of 261 glaucomatous patients had been included in our *** the mean IOP and the number of IOP-lowering medications were significantly decreased from 32.9±12.0 to 16.4±5.7 mm Hg(P<0.0001)and 3.0±0.9 to 0.9±1.0(P<0.0001),respectively,at the last *** cumulative complete success rate and qualified success rate were 77.8%and 92.0%at 1-year follow-up,and 47.2%and 77.7%at 3-year follow *** were no significant differences in surgical outcomes between primary angle-closure glaucoma(PACG)and primary open angle glaucoma(POAG).In PACG patients,the success rates of trabeculectomy were comparable with those of ***(HR=1.904,P=0.011),encapsulated bleb(HR=2.756,P<0.001),and more preoperative topical medications(HR=2.475,P=0.008)were risk factors for surgical ***:The qualified success rate of trabeculectomy with MMC in glaucomatous patients in the cohort is 92.0%at 1-year,and 77.7%at 3-year follow ***,encapsulated bleb,and more preoperative topical medications are associated with surgical failure.

关键词： glaucoma trabeculectomy outcomes risk factors

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Perineuronal nets increase inhibitory GABAergic currents during the critical period in rats

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 120-125页

作者： Hui Liu Peng-Fen Gao Hai-Wei Xu Ming-Ming Liu Tao Yu Jun-Ping Yao Zheng-Qin Yin Southwest Eye Hospital Southwest Hospital Third Military Medical University key lab of visual damage and regeneration & restoration of chongqing

AIM: To investigate inhibitory γ-aminobutyric acid (GABA) ergic postsynaptic currents (IPSCs) and postsynaptic currents (PSCs) in layer IV of the rat visual cortex during the critical period and when plasticity was extended through dissolution of the perineuronal nets (PNNs). METHODS: We employed 24 normal Long-Evans rats to study GABA A-PSC characteristics of neurons within layer IV of the visual cortex during development. The animals were divided into six groups of four rats according to ages at recording: PW3 (P21 -23d), PW4 (P28 -30d), PW5 (P35-37d), PW6 (P42-44d), PW7 (P49-51d), and PW8 (56-58d). An additional 24 chondroitin sulfate proteoglycan (CSPG) degradation rats (also Long-Evans) were generated by making a pattern of injections of chondroitinase ABC (chABC) into the visual cortex 1 week prior to recording at PW3, PW4, PW5, PW6, PW7, and PW8. Immunohistochemistry was used to identify the effect of chABC injection on CSPGs. PSCs were detected with whole-cell patch recordings, and GABA A receptor-mediated IPSCs were pharmacologically isolated. RESULTS: IPSC peak current showed a strong rise in the age-matched control group, peaked at PW5 and were maintained at a roughly constant value thereafter. Although there was a small increase in peak current for the chABC group with age, the peak currents continued to decrease with the delayed highest value at PW6, resulting in significantly different week-by-week com-parison with normal development. IPSC decay time continued to increase until PW7 in the control group, while those in the chABC group were maintained at astable level after an initial increase at PW4. Compared with normal rats, the decay times recorded in the chABC rats were always shorter, which differed significantly at each age. We did not observe any differences in IPSC properties between the age-matched control and penicillinase (P-ase) group. However, the change in IPSCs after chABC treatment was not reflected in the total PSCs or in basic membrane

关键词： gamma-aminobutyric acid receptor plasticity visual cortex development postsynaptic currents chondroitinase ABC chondroitin sulfate proteoglycans whole-cell patch recording

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Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

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Neural regeneration Research 2015年第10期10卷 1622-1627页

作者： Bing-bing Guo Xiao-lin Zheng Zhen-gang Lu Xing Wang Zheng-qin Yin Wen-sheng Hou Ming Meng Department of Biomedical Engineering Chongqing University Department of Psychological and Brain Sciences Dartmouth College key lab of visual damage and regeneration & restoration Third Military Medical University

visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only ＂see＂ pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex（the implant area） is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine（LSVM） as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.

关键词： nerve regeneration primary visual cortex electrical stimulation visual cortical prosthesis low resolution vision pixelized image functional magnetic resonance imaging voxel size neural regeneration brain activation pattern

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Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

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International Journal of Ophthalmology(English edition) 2016年第7期9卷 955-966页

作者： Wei-Yang Shao Xiao Liu Xian-Liang Gu Xi Ying Nan Wu Hai-Wei Xu Yi Wang Southwest Hospital/Southwest Eye Hospital Third Military Medical University Chongqing 400038 China key lab of visual damage and regeneration & restoration of chongqing Chongqing 400038 China

AIM：To explore the effects of αA-crystallin in astrocyte gliosis after optic nerve crush（ONC） and the mechanism of α-crystallin in neuroprotection and axon ***：ONC was established on the SpragueDawley rat model and αA-crystallin（10 -4 g/L,4 μL） was intravitreously injected into the rat ***-visual evoked potential（F-VEP） was examined 14 d after ONC,and the glial fibrillary acidic protein（GFAP） levels in the retina and crush site were analyzed 1,3,5,7 and 14 d after ONC by immunohistochemistry（IHC） and Western blot *** levels of beta Tubulin（TUJ1）,growth-associated membrane phosphoprotein-43（GAP-43）,chondroitin sulfate proteoglycans（CSPGs） and neurocan were also determined by IHC 14 d after ***：GFAP level in the retina and the optic nerve significantly increased 1d after ONC,and reached the peak level 7d *** of αA-crystallin significantly decreased GFAP level in both the retina and the crush site 3d after ONC,and induced astrocytes architecture remodeling at the crush *** of retinal ganglion cell（RGC） axons indicated αAcrystallin markedly promoted axon regeneration in ONC rats and enhanced the regenerated axons penetrated into the glial *** and neurocan expression also decreased 14 d after αA-crystallin *** amplitude（N1-P1） and latency（P1） of F-VEP were also ***：Our results suggest α-crystallin promotes the axon regeneration of RGCs and suppresses the activation of astrocytes.

关键词： αA-crystallin axonal regeneration astrocyte glial scar chondroitin sulfate proteoglycans optic nerve crush

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