Experimental eye research最新文献_第2页

METTL16 promotes corneal nerve regeneration in diabetic corneal neuropathy METTL16促进糖尿病角膜神经病变角膜神经再生。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-08 DOI: 10.1016/j.exer.2025.110514

Yuan Zhang , Bin Jiang , Nan Zhang , Cheng Lai , Yilong Zhang , Jiaqi Han , Zeli Tang , Yang Liu , Min Ke

{"title":"METTL16 promotes corneal nerve regeneration in diabetic corneal neuropathy","authors":"Yuan Zhang , Bin Jiang , Nan Zhang , Cheng Lai , Yilong Zhang , Jiaqi Han , Zeli Tang , Yang Liu , Min Ke","doi":"10.1016/j.exer.2025.110514","DOIUrl":"10.1016/j.exer.2025.110514","url":null,"abstract":"<div><div>As a leading ocular disorder caused by diabetes mellitus, diabetic corneal neuropathy (DCN) is characterized by decreased corneal sensation, ocular irritation, delayed corneal wound healing and corneal neuropathic pain. Several researchers including us previously evidenced that DCN is regulated by several transcriptional and/or epigenetic factors. However, the role of N6-methyladenosine (m6A) modification, the most common internal modification in eukaryotic RNAs, in the pathogenesis of DCN remains largely unexplored. In the current work, we aimed to elucidate the pathological role of m6A modification in DCN. Using an m6A epitranscriptomic microarray, we identified differentially m6A-modified mRNAs in DCN. Additionally, we identified a significant decrease in the expression of methyltransferase-Like Protein 16 (METTL16) in trigeminal ganglion (TG) tissues of diabetic mice. Notably, using corneal epithelial nerve injury model and subconjunctival injection of adeno-associated virus, we demonstrated that activation of METTL16 promotes corneal nerve regeneration and accelerates corneal wound healing in DCN mice, suggesting the therapeutic potential of METTL16 in DCN. Moreover, by multi-omics approach, correlation analysis and experimental verification, we identified <em>P4ha1</em>, <em>Pcm1</em>, <em>Ccnd1</em> and <em>Hsph1</em> as potential targets of METTL16, revealing the molecular mechanism mediated by METTL16. We also observed a reduction in METTL16 levels in the peripheral blood of diabetic patients, indicating that METTL16 may serve as a potential biomarker for disorders associated with hyperglycemia. In light of these results, aberrant regulation of METTL16 may represent one of the pathogenic mechanisms underlying DCN and could serve as a potential therapeutic target for its treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110514"},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defining spaceflight associated dry eye syndrome (SADES): Mechanisms, complications, and countermeasures 定义航天相关干眼综合征（SADES）：机制、并发症和对策

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-07 DOI: 10.1016/j.exer.2025.110513

Ryung Lee , Joshua Ong , Ethan Waisberg , Alex Suh , Mehmet Kadipasaoglu , Thomas Mader , Charles R. Gibson , John Berdahl , Andrew G. Lee

{"title":"Defining spaceflight associated dry eye syndrome (SADES): Mechanisms, complications, and countermeasures","authors":"Ryung Lee , Joshua Ong , Ethan Waisberg , Alex Suh , Mehmet Kadipasaoglu , Thomas Mader , Charles R. Gibson , John Berdahl , Andrew G. Lee","doi":"10.1016/j.exer.2025.110513","DOIUrl":"10.1016/j.exer.2025.110513","url":null,"abstract":"<div><div>There is a high prevalence of dry eye-related symptoms among astronauts during spaceflight. We propose naming this phenomenon: Spaceflight Associated Dry Eye Syndrome (SADES). In this study, we review the potential mechanisms of dry eye in the spaceflight environment, categorizing them into external (radiation, environmental hazards) and microgravity-related (meibum outflow) mechanisms. One key mechanism is that microgravity impedes the secretion of meibum, the primary contributor to the tear film lipid layer. SADES may impact the ocular surface due to the positive feedback loop of inflammation and tear film irregularities. These changes may lead to corneal epithelial defects, keratitis, decreased vision, and an increased potential for corneal thinning and perforation. We discuss available countermeasures to combat SADES, propose a new set of applicable technologies, and review appropriate medications for its prevention and treatment. This topic may be of significant interest to ophthalmologists as many of the established terrestrial mechanisms, diagnosis, and management of dry eye syndrome apply to the extreme environment of spaceflight.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110513"},"PeriodicalIF":3.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Curcumin Ameliorates Benzalkonium Chloride-Induced Dry Eye Disease in Mice. 姜黄素改善苯扎氯铵引起的小鼠干眼病。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-07 DOI: 10.1016/j.exer.2025.110509

Ziyu Liua, Yaqiong Li, Ya Wen, Jiayu Bao, Lei Tian, Ying Jie

引用次数: 0

Human corneal epithelial cells harvested from advanced surface ablation (ASA): An optimized in vitro culture protocol 从高级表面消融（ASA）中收获的人角膜上皮细胞：一种优化的体外培养方案。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-05 DOI: 10.1016/j.exer.2025.110510

Helen Gutiérrez , Antonio López-García , Miguel J. Maldonado , Laura García-Posadas

{"title":"Human corneal epithelial cells harvested from advanced surface ablation (ASA): An optimized in vitro culture protocol","authors":"Helen Gutiérrez , Antonio López-García , Miguel J. Maldonado , Laura García-Posadas","doi":"10.1016/j.exer.2025.110510","DOIUrl":"10.1016/j.exer.2025.110510","url":null,"abstract":"<div><h3>Purpose</h3><div>Corneal epithelial cells obtained from advanced surface ablation (ASA) surgery provide a valuable resource for <em>in vitro</em> models of ocular surface diseases. The aim of this study is to enhance culture conditions and characterize the functionality of EpiASA cells in culture, focusing on their ability to keep the distinctive properties of corneal epithelial cells.</div></div><div><h3>Methods</h3><div>EpiASA samples from 51 patients were included in the study. Two different collection media were tested, and their effect on sample preservation and initial viability was evaluated. Then, cells were disaggregated and cultured using different strategies to increase cell viability, which was measured by AlamarBlue assay. Once the optimized conditions were established, cells were cultured and passaged, and structural and functional characterization of native tissue, primary cultures, and first-passage cultures was performed using atomic force microscopy (AFM), qPCR, and immunofluorescence stainings.</div></div><div><h3>Results</h3><div>The addition of trehalose to the basal collection medium increased EpiASA initial viability. Culture surface coating with type I collagen, along with the supplementation of culture medium with hydrocortisone, significantly increased cell viability. On the contrary, co-cultures with different ocular cell lines, or the use of human serum, did not provide a sustained benefit. Further low-concentration trehalose supplementation of EpiASA cultures enhanced monolayer formation and allowed subculturing. AFM and immunofluorescence confirmed that passage 1 EpiASA cells retained corneal epithelial characteristics, including well-organized microvilli and uniform expression of barrier and epithelial markers.</div></div><div><h3>Conclusion</h3><div>This research provides an optimized protocol (EpiKeraMAX) for using EpiASA samples for <em>in vitro</em> studies of human corneal cells.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110510"},"PeriodicalIF":3.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA H19 and miR-138 modulate retinal neovascularization and associated pathological features in hypoxia-induced disease models LncRNA H19和miR-138在缺氧诱导的疾病模型中调节视网膜新生血管和相关病理特征。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-05 DOI: 10.1016/j.exer.2025.110512

Yong Yu , Yu Di , Peijie Li , Qingzhu Nie , Xiaolong Chen , Aiyuan Wang , Kaiming Ren

{"title":"LncRNA H19 and miR-138 modulate retinal neovascularization and associated pathological features in hypoxia-induced disease models","authors":"Yong Yu , Yu Di , Peijie Li , Qingzhu Nie , Xiaolong Chen , Aiyuan Wang , Kaiming Ren","doi":"10.1016/j.exer.2025.110512","DOIUrl":"10.1016/j.exer.2025.110512","url":null,"abstract":"<div><div>In this study, we investigated the mechanism of action of the long noncoding RNA (lncRNA) H19 to evaluate potential novel therapeutic targets in retinal neovascular diseases. Following establishment of an oxygen-induced mouse retinopathy (OIR) model, we knocked down lncRNA H19 and microRNA (miR)-138 by intravitreal injection of adenovirus and assessed the outcomes of interference and overexpression by real time quantitative polymerase chain reaction (RT-qPCR). Additionally, we observed vascular lesions of the retina by hematoxylin and eosin staining and retinal paving staining and detected the expression of relevant factors by Western blot, immunohistochemistry, and immunofluorescence. Human retinal endothelial cells (HREC) were cultured and hypoxia models constructed using hypoxia-treated cells to explore the <em>in vitro</em> effects of knockdown and overexpression of lncRNA H19 and miR-138 in hypoxia-treated cells by RT-qPCR. Moreover, we assessed cell migration, proliferation, and cell cycle progression, as well as relationships between lncRNA H19, vascular endothelial growth factor (VEGF), and miR-138.Our experimental results demonstrated significantly upregulated expression of lncRNA H19 and downregulated miR-138 levels in both oxygen-induced retinopathy (OIR) mouse models and hypoxic human retinal endothelial cells (HRECs). Moreover, lncRNA H19 knockdown and miR-138 overexpression reduced pathological changes in the retina and decreased VEGF and hypoxia-inducible factor (HIF)-1α levels. Furthermore, luciferase assays demonstrated targeted binding of miR-138 to sites on H19 and <em>HIF1α</em>. These findings indicated that expression of miR-138 can reduce HIF-1α and H19 levels both directly and through competitive adsorption by H19 and thereby participate in regulating retinal neovascularization.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110512"},"PeriodicalIF":3.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Machine learning reveals ATM and CNOT6L as critical factors in cataract pathogenesis" [Exp. Eye Res. 257 (2025) 110448]. “机器学习揭示ATM和CNOT6L是白内障发病的关键因素”[j].眼科杂志，257(2025)110448。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-04 DOI: 10.1016/j.exer.2025.110488

Peng Qi, Songhao Zhang, Wenbing Guo, Chao Liu

引用次数: 0

Single-cell RNA sequencing reveals the role of heat shock protein 90AA1 in Müller cell proliferation via the Necroptosis/MAPK pathway in diabetic retinopathy 单细胞RNA测序揭示了热休克蛋白90AA1通过坏死性下垂/MAPK通路在糖尿病视网膜病变中<s:1> ller细胞增殖中的作用。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-03 DOI: 10.1016/j.exer.2025.110508

Ying Yan , Hongjian Yang , Qiaonuo Wei , Doudou Yu , Chengyuan Gao , Bo Diao , Yanping Song , Xiao Chen

{"title":"Single-cell RNA sequencing reveals the role of heat shock protein 90AA1 in Müller cell proliferation via the Necroptosis/MAPK pathway in diabetic retinopathy","authors":"Ying Yan , Hongjian Yang , Qiaonuo Wei , Doudou Yu , Chengyuan Gao , Bo Diao , Yanping Song , Xiao Chen","doi":"10.1016/j.exer.2025.110508","DOIUrl":"10.1016/j.exer.2025.110508","url":null,"abstract":"<div><div>This study investigates the role of heat shock protein 90AA1 (HSP90AA1) in the proliferation of Müller cells (MCs) within the context of diabetic retinopathy (DR). Using single-cell RNA sequencing (scRNA-seq) on retinal samples from four diabetic and two nondiabetic patients, we integrated bioinformatics analyses with experimental exploration using in vivo and in vitro DR models to investigate MC pathogenesis in DR. Our findings identified nine major retinal cell types and elucidated how diabetes disrupts retinal cell type composition, gene expression profiles, and intercellular communication. HSP90AA1, significantly downregulated in the MCs of the diabetic patients, emerged as a potential hub gene, with its associated pathways involving necroptosis (RIP1/RIP3/MLKL) and mitogen-activated protein kinase (MAPK) signaling. Furthermore, our results from DR models suggeste that the downregulation of HSP90AA1 may induce DR-related MC proliferation. This study provides novel insights into the cellular and molecular mechanisms underlying DR, highlighting the suppressive role of HSP90AA1 in MC proliferation as a promising therapeutic target for DR.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110508"},"PeriodicalIF":3.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating prolactin-induced protein and its role in modulating the metabolic state of the keratoconus microenvironment 研究催乳素诱导蛋白及其在圆锥角膜微环境代谢状态调节中的作用

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-02 DOI: 10.1016/j.exer.2025.110507

Wentao Liang , Brenda Vasini , Joseph Clayton , Jian-Xing Ma , Dimitrios Karamichos

{"title":"Investigating prolactin-induced protein and its role in modulating the metabolic state of the keratoconus microenvironment","authors":"Wentao Liang , Brenda Vasini , Joseph Clayton , Jian-Xing Ma , Dimitrios Karamichos","doi":"10.1016/j.exer.2025.110507","DOIUrl":"10.1016/j.exer.2025.110507","url":null,"abstract":"<div><div>Keratoconus (KC) is a progressive corneal disorder characterized by thinning and irregular astigmatism, leading to visual impairment. This study investigates the role of Prolactin-Induced Protein (PIP), a 17-kDa glycoprotein significantly downregulated in KC subjects, in modulating corneal cellular metabolism. Using human corneal fibroblasts from healthy (HCFs) and KC (HKCs) subjects, we assessed the effects of exogenous PIP (50–500 ng/mL) via targeted mass spectrometry and Seahorse bioenergetic analyses. Metabolomic profiling revealed that PIP significantly modulates various metabolites involved in multiple bioenergetic and oxidative stress related pathways including the Warburg effect and thiamine metabolism. Seahorse analysis revealed that when compared to HCFs, HKCs exhibit impaired ATP production from both oxidative phosphorylation and glycolysis. Notably, PIP treatment reversed this impairment and selectively enhanced mitochondrial function and glycolysis in HKCs without affecting HCFs. This study provides the first evidence of PIP's role in regulating energy metabolism in KC, suggesting its potential as a therapeutic target for addressing the metabolic dysfunction underlying KC pathogenesis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110507"},"PeriodicalIF":3.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Doxycycline mitigates corneal fibrosis by suppressing the focal adhesion pathway 强力霉素通过抑制局灶性粘附途径减轻角膜纤维化。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-02 DOI: 10.1016/j.exer.2025.110506

Jiaxin Zhou, Bingbing He, Wenjin Zou

引用次数: 0

Human induced pluripotent stem cell-derived extracellular vesicles promote neuroprotection effects in rat optic nerve crush model 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

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-01 DOI: 10.1016/j.exer.2025.110505

Yuezhu Lu , Miao Guo , Yuming Liu , Haotian Liu , Mengyu Liao , Kai He , Xue Dong , Tian Wang , Heng Wang , Yong Zhong , Hua Yan

{"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":"10.1016/j.exer.2025.110505","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":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0