Experimental eye research最新文献

Targeting pericytes in the retina: characterization of the inducible NG2-CreERT2 knock-in mouse model. 靶向视网膜周细胞：诱导型NG2-CreERT2敲入小鼠模型的表征。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-15 DOI: 10.1016/j.exer.2025.110519

Julia Preishuber-Pflügl, Susanne Maria Brunner, Wenhui Huang, Andreas Koller, Herbert A Reitsamer, Andrea Trost

{"title":"Targeting pericytes in the retina: characterization of the inducible NG2-CreERT2 knock-in mouse model.","authors":"Julia Preishuber-Pflügl, Susanne Maria Brunner, Wenhui Huang, Andreas Koller, Herbert A Reitsamer, Andrea Trost","doi":"10.1016/j.exer.2025.110519","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110519","url":null,"abstract":"<p><p>Pericytes (PCs) are mural cells embedded in a common basement membrane with endothelial cells (ECs) on capillaries. They are key players in the regulation of stability and function of blood vessels and are an essential component of the blood-brain and blood-retinal barrier. In addition, PCs are reported to be involved in wound healing and tissue regeneration and represent a promising target for the modulation of scarring processes. Due to their heterogeneous expression pattern, a single specific molecular marker for PCs remains elusive. Inducible reporter mouse models represent a frequently used tool for tracing the fate of a specific cell type, via the expression of a fluorescence reporter protein in the target cell following tamoxifen (TAM) induction. In a recent study, we characterized the TAM-inducible reporter mouse model NG2-CreERTM-tdTomato and demonstrated specific but marginal PC labeling in the retinal capillary plexuses with mean values ranging from 21.9 to 35.5 %. Since such a low labeling efficiency is not sufficient for reliable cell tracing, we characterized a TAM-inducible Cre mouse model expressing the enhanced estrogen receptor ERT2 in the present work. The NG2-CreERT2 knock-in mouse was crossbred with the tdTomato Ai9 reporter mouse to assess efficiency of PC labeling in the retina. The expression of tdTomato was restricted to mural cells, labeling vascular smooth muscle cells on larger vessels and PCs on capillaries. The use of the CreERT2 mouse resulted in an increased percentage of labeled PCs in the superficial layer of the retina with mean values ranging from 68.5 to 70.2 %.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"110519"},"PeriodicalIF":3.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648937","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

Imaging Techniques for the Detection of Choroidal Neovascularization. 脉络膜新生血管检测的影像学技术。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-14 DOI: 10.1016/j.exer.2025.110522

Mi Zheng, Yannis M Paulus

{"title":"Imaging Techniques for the Detection of Choroidal Neovascularization.","authors":"Mi Zheng, Yannis M Paulus","doi":"10.1016/j.exer.2025.110522","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110522","url":null,"abstract":"<p><p>Choroidal neovascularization (CNV) has been associated with a wide variety of chorioretinal disorders, which can cause vascular leakage, bleeding, and scar formation, leading to significant vision loss. The effective and precise detection of CNV is essential for optimal disease management. A classification system has been devised to categorize neovascularization according to its anatomical location. The system distinguishes three distinct types of neovascularization: type 1, type 2, and type 3. According to the exudative features of the new vessels, CNV can be divided into exudative and non-exudative categories. Each type of CNV exhibits unique features across various imaging modalities. The present study reviews contemporary imaging modalities employed in the detection of CNV, with a focus on the underlying mechanisms, their respective advantages and disadvantages, their typical clinical utilization, and the characteristic features of CNV that are discernible through these techniques. The exploration of novel promising imaging techniques for CNV detection including photoacoustic microscopy, AI, photothermal OCT, and functional fluorescent angiography is also performed.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110522"},"PeriodicalIF":3.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648936","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

Differential Expression Profiles of MAPT (TAU ) Gene Isoforms in Dry Age-Related Macular Degeneration. 干性年龄相关性黄斑变性中MAPT （TAU）基因亚型的差异表达谱

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-11 DOI: 10.1016/j.exer.2025.110517

Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila Soheili, Fatemeh Suri

{"title":"Differential Expression Profiles of MAPT (TAU ) Gene Isoforms in Dry Age-Related Macular Degeneration.","authors":"Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila Soheili, Fatemeh Suri","doi":"10.1016/j.exer.2025.110517","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110517","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a neurodegenerative retinal disorder that typically emerges later in life and is the primary cause of central visual loss. The microtubule-associated protein Tau (MAPT) gene produces six significant splice variants in neural cells, which are differentiated by the exclusion or inclusion of exon 10, resulting in expression of 3R and 4R isoforms. Changes in Tau expression and the ratio of 4R to 3R isoforms have been observed in various neurodegenerative diseases; however, the expression of Tau mRNA in AMD remains unexplored. This study represents the first investigation into the expression of MAPT transcript variants in patients with dry AMD. Human donor eyes were sourced from the Iranian Eye Bank and divided into three categories: Dry-AMD (aged ≥50 years, n=13), Elderly-Normal (aged ≥50 years, n=13), and Young-Normal (aged ≤40 years, n=10). Retinal RNA was isolated, and quantitative real-time PCR (qRT-PCR) was employed to evaluate total Tau, as well as the 3R, and 4R transcript variants using specific primers. Dry-AMD samples showed a mixture of 3R and 4R isoforms, with no significant difference in total Tau levels when compared to both control groups. However, the 4R/3R ratio was significantly higher in Dry-AMD samples compared to both control groups, while no significant difference was observed between elderly and young controls. These findings indicate that changes in the 4R/3R Tau ratio may play a role in the progression of Dry-AMD, potentially triggering pathways that promote disease advancement. Further research is necessary to explore these results across various stages of the disease.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110517"},"PeriodicalIF":3.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625610","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

Hypoxia-Induced Activation of Calpain and Oxidative Stress in Mitochondria Leads to RGC Death in Human iPSC-derived Retinal Organoids. 缺氧诱导的线粒体钙蛋白酶激活和氧化应激导致人类ipsc来源的视网膜类器官RGC死亡。

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-10 DOI: 10.1016/j.exer.2025.110511

Masayuki Hirata, Yayoi Kishimoto, Thomas R Shearer, Mitsuyoshi Azuma

{"title":"Hypoxia-Induced Activation of Calpain and Oxidative Stress in Mitochondria Leads to RGC Death in Human iPSC-derived Retinal Organoids.","authors":"Masayuki Hirata, Yayoi Kishimoto, Thomas R Shearer, Mitsuyoshi Azuma","doi":"10.1016/j.exer.2025.110511","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110511","url":null,"abstract":"<p><p>Proteolysis by calpain enzyme contributes to retinal ganglion cell (RGC) death in hypoxic monkey and human retinal explants, although the mechanism is not fully understood yet. The present experiments are to determine if calpain activation in mitochondria and the subsequent oxidative stress were underlying mechanism driving RGC death in a hypoxia/regeneration culture model, using retinal organoids derived from human induced pluripotent stem (iPS) cells. Retinal organoids were differentiated from human iPS cells. RGCs labeled with tdTomato were purified with magnetic-activated cell sorting. Cellular localization of calpain-related proteins was observed by immunohistochemistry. For example, α-spectrin breakdown product 150 (SBDP150) was detected as a marker for cytosolic calpain activation. Retinal organoids and purified RGCs were cultured with or without calcium chelator BAPTA, calpain inhibitor SNJ-1945, or NRF2 activator NK252 under hypoxia/reoxygenation. Truncated apoptosis-inducing factor (tAIF), a marker for mitochondrial calpain activation was determined by immunoblotting. Mitochondrial membrane potential (MMP) was measured with MT-1 dye. Thiol levels were assessed with Thiol Assay Kit. Hypoxia/reoxygenation induced an increase in the cytoplasmic calpain activation marker SBDP150 and the mitochondrial calpain activation marker tAIF, leading to RGC death. Additionally, it led to a decrease in thiol levels and MMP impairment. These changes were inhibited by BAPTA and calpain inhibitor SNJ-1945. NK252 prevented RGC death but did not inhibit calpain-mediated proteolysis. Our findings with human iPS-drived RGC culture model demonstrate that calcium influx in hypoxic RGCs activates mitochondrial calpain, which induced the depletion of thiol levels and the collapse of MMP, ultimately leading to cell death.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110511"},"PeriodicalIF":3.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616907","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

Treatment of nitrogen mustard-induced corneal injury with alpha-melanocyte stimulating hormone α -黑色素细胞刺激激素治疗氮芥诱导的角膜损伤

IF 3 2区医学

Experimental eye research Pub Date : 2025-07-08 DOI: 10.1016/j.exer.2025.110515

Francesca Kahale , Pier Luigi Surico , Rohan Bir Singh, Parisa Dashti, Swatilekha Hazra, Shilpy Bhullar, Jia Yin, Yihe Chen, Reza Dana

{"title":"Treatment of nitrogen mustard-induced corneal injury with alpha-melanocyte stimulating hormone","authors":"Francesca Kahale , Pier Luigi Surico , Rohan Bir Singh, Parisa Dashti, Swatilekha Hazra, Shilpy Bhullar, Jia Yin, Yihe Chen, Reza Dana","doi":"10.1016/j.exer.2025.110515","DOIUrl":"10.1016/j.exer.2025.110515","url":null,"abstract":"<div><div>Nitrogen mustard (NM) exposure leads to severe corneal damage, resulting in persistent corneal inflammation, epithelial damage, endothelial dysfunction, and vision impairment. Effective therapeutic strategies to mitigate these effects remain limited. This study evaluates the protective effects of alpha-melanocyte-stimulating hormone (α-MSH) in a murine model of NM-induced corneal injury. C57BL/6 mice were exposed to NM and treated with systemic α-MSH for 28 days. Clinical assessments, histological analysis, anterior segment optical coherence tomography (AS-OCT), and immunohistochemistry were performed to evaluate corneal integrity, inflammation, and cell survival. α-MSH treatment significantly reduced corneal epitheliopathy, prevented epithelial thinning, and preserved limbal epithelial cell density compared to untreated controls. Central stromal thickness was significantly lower in α-MSH-treated mice, suggesting reduced corneal edema. Endothelial cell morphology was preserved, with higher endothelial cell density, reduced coefficient of variation, and improved hexagonality in treated mice. TUNEL assay demonstrated significantly lower apoptosis in both central and limbal corneal regions at early (day 7) and late (day 28) time points in α-MSH-treated eyes. These findings highlight the cytoprotective and anti-inflammatory effects of α-MSH. By mitigating NM-induced injury, α-MSH preserves corneal structural integrity and function, demonstrating its potential as a therapeutic intervention for mustard gas keratopathy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110515"},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588827","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

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