Yuezhu Lu , Miao Guo , Yuming Liu , Haotian Liu , Mengyu Liao , Kai He , Xue Dong , Tian Wang , Heng Wang , Yong Zhong , Hua Yan
{"title":"人诱导多能干细胞来源的细胞外囊泡促进大鼠视神经损伤模型的神经保护作用","authors":"Yuezhu Lu , Miao Guo , Yuming Liu , Haotian Liu , Mengyu Liao , Kai He , Xue Dong , Tian Wang , Heng Wang , Yong Zhong , Hua Yan","doi":"10.1016/j.exer.2025.110505","DOIUrl":null,"url":null,"abstract":"<div><div>Optic neuropathies significantly contribute to permanent vision loss, frequently characterized by the deterioration of retinal ganglion cells (RGCs) and axonal loss. Current therapeutic strategies remain insufficient. Induced pluripotent stem cell-derived extracellular vesicles (iPSC-EVs) have surfaced as a compelling substitute for stem cell therapies. Our study evaluates the neuroprotective effects of iPSC-EVs in a rat optic nerve crush (ONC) model. iPSC-EVs were isolated and characterized. The intravitreal (IVT) injections of iPSC-EVs or PBS were performed. RGCs survival was assessed at 7 and 14 days post-injury. Axonal regeneration was evaluated via anterograde labeling. Apoptosis of RGCs was detected using TUNEL assay. Retinal morphological changes and visual function recovery were assessed. Transcriptomic changes in the retina were analyzed by RNA sequencing to investigate potential underlying mechanisms. Additionally, Western blot was conducted to evaluate the expression levels of components in the phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) pathway. The IVT injections of iPSC-EVs significantly improved RGCs survival and reduced neuronal apoptosis. Optical coherence tomography (OCT) revealed preservation of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, alongside reduced optic nerve atrophy. Functional recovery was evidenced by F-VEP and axonal regeneration was detected. Mechanistically, RNA sequencing and Western blot implicated the stimulation of the PI3K/AKT pathway. Our study shows that iPSC-EVs exert significant neuroprotective and regenerative effects in a rat ONC model, underscoring their promise as a novel treatment candidate for optic neuropathies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110505"},"PeriodicalIF":3.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Human induced pluripotent stem cell-derived extracellular vesicles promote neuroprotection effects in rat optic nerve crush model\",\"authors\":\"Yuezhu Lu , Miao Guo , Yuming Liu , Haotian Liu , Mengyu Liao , Kai He , Xue Dong , Tian Wang , Heng Wang , Yong Zhong , Hua Yan\",\"doi\":\"10.1016/j.exer.2025.110505\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Optic neuropathies significantly contribute to permanent vision loss, frequently characterized by the deterioration of retinal ganglion cells (RGCs) and axonal loss. Current therapeutic strategies remain insufficient. Induced pluripotent stem cell-derived extracellular vesicles (iPSC-EVs) have surfaced as a compelling substitute for stem cell therapies. Our study evaluates the neuroprotective effects of iPSC-EVs in a rat optic nerve crush (ONC) model. iPSC-EVs were isolated and characterized. The intravitreal (IVT) injections of iPSC-EVs or PBS were performed. RGCs survival was assessed at 7 and 14 days post-injury. Axonal regeneration was evaluated via anterograde labeling. Apoptosis of RGCs was detected using TUNEL assay. Retinal morphological changes and visual function recovery were assessed. Transcriptomic changes in the retina were analyzed by RNA sequencing to investigate potential underlying mechanisms. Additionally, Western blot was conducted to evaluate the expression levels of components in the phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) pathway. The IVT injections of iPSC-EVs significantly improved RGCs survival and reduced neuronal apoptosis. Optical coherence tomography (OCT) revealed preservation of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, alongside reduced optic nerve atrophy. Functional recovery was evidenced by F-VEP and axonal regeneration was detected. Mechanistically, RNA sequencing and Western blot implicated the stimulation of the PI3K/AKT pathway. Our study shows that iPSC-EVs exert significant neuroprotective and regenerative effects in a rat ONC model, underscoring their promise as a novel treatment candidate for optic neuropathies.</div></div>\",\"PeriodicalId\":12177,\"journal\":{\"name\":\"Experimental eye research\",\"volume\":\"258 \",\"pages\":\"Article 110505\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental eye research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014483525002763\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental eye research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014483525002763","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Human induced pluripotent stem cell-derived extracellular vesicles promote neuroprotection effects in rat optic nerve crush model
Optic neuropathies significantly contribute to permanent vision loss, frequently characterized by the deterioration of retinal ganglion cells (RGCs) and axonal loss. Current therapeutic strategies remain insufficient. Induced pluripotent stem cell-derived extracellular vesicles (iPSC-EVs) have surfaced as a compelling substitute for stem cell therapies. Our study evaluates the neuroprotective effects of iPSC-EVs in a rat optic nerve crush (ONC) model. iPSC-EVs were isolated and characterized. The intravitreal (IVT) injections of iPSC-EVs or PBS were performed. RGCs survival was assessed at 7 and 14 days post-injury. Axonal regeneration was evaluated via anterograde labeling. Apoptosis of RGCs was detected using TUNEL assay. Retinal morphological changes and visual function recovery were assessed. Transcriptomic changes in the retina were analyzed by RNA sequencing to investigate potential underlying mechanisms. Additionally, Western blot was conducted to evaluate the expression levels of components in the phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) pathway. The IVT injections of iPSC-EVs significantly improved RGCs survival and reduced neuronal apoptosis. Optical coherence tomography (OCT) revealed preservation of retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, alongside reduced optic nerve atrophy. Functional recovery was evidenced by F-VEP and axonal regeneration was detected. Mechanistically, RNA sequencing and Western blot implicated the stimulation of the PI3K/AKT pathway. Our study shows that iPSC-EVs exert significant neuroprotective and regenerative effects in a rat ONC model, underscoring their promise as a novel treatment candidate for optic neuropathies.
期刊介绍:
The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.