Experimental eye research最新文献

{"title":"Pharmacological depletion of pericytes induces diabetic retinopathy-like abnormal blood vessels in neonatal rat retina","authors":"Kenta Otsuka,&nbsp;Akane Morita,&nbsp;Toshihide Kashihara,&nbsp;Tsutomu Nakahara","doi":"10.1016/j.exer.2025.110243","DOIUrl":"10.1016/j.exer.2025.110243","url":null,"abstract":"<div><div>Diabetic retinopathy is a major ocular complication associated with diabetes mellitus. Pericyte loss is a hallmark of diabetic retinopathy. The platelet-derived growth factor (PDGF)-B-PDGF receptor-β (PDGFRβ) signaling pathway plays an important role in the proliferation and migration of pericytes. Imatinib, an antineoplastic drug primarily used to treat chronic myelogenous leukemia, inhibits the PDGFRβ tyrosine kinase. In this study, we aimed to determine the time-course of pathological changes in the retinal vasculature following pharmacological depletion of pericytes with imatinib. Rats were injected with imatinib once daily for 1, 2, or 4 days starting on postnatal day (P) 4. The distribution of endothelial cells and pericytes in the retina was assessed at P4, P5, P6, P8, and P11. Single and multiple injections of imatinib (100 mg/kg) significantly decreased the pericyte coverage within the retinal capillaries on the day after the completion of each injection protocol. After pericyte coverage decreased, endothelial cell degeneration and microaneurysm formation were initiated. Following the elimination of the inhibitory effect of imatinib on the PDGFRβ signaling pathway, the pericyte coverage returned to control levels but structural abnormalities of the retinal vasculature with microaneurysms and dense capillaries were observed. Vascular pathological features are similar to those of the early clinical manifestations of diabetic retinopathy. Therefore, these rats could serve as animal models to study the mechanisms underlying the pathological changes that occur after pericyte loss in diabetic retinopathy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110243"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002444","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}

{"title":"Establishment and evaluation of rabbit model for corneal ectasia by photorefractive keratectomy","authors":"Lin Ye ,&nbsp;Yongjiu Lv ,&nbsp;Chenli Feng ,&nbsp;Jiayue Yuan ,&nbsp;Xueqi Lin ,&nbsp;Qianhong Feng ,&nbsp;Shunmei Ji ,&nbsp;Wei Wu ,&nbsp;Jinhui Dai","doi":"10.1016/j.exer.2025.110248","DOIUrl":"10.1016/j.exer.2025.110248","url":null,"abstract":"<div><div>The study aimed to compare the effects of different types of excimer laser keratectomy on rabbit corneas and to identify the optimal disease model for corneal ectasia. Additionally, investigating the structural and molecular alterations in the novel disease model helped explore the mechanisms underlying biomechanical cues in corneal ectasia. 2.0–2.5 kg New Zealand white rabbits were treated with different types of excimer laser keratectomy, including comparisons between photorefractive keratectomy (PRK) and phototherapeutic keratectomy (PTK) surgeries, as well as comparisons of different ablation depths of PRK. Detailed tests on post-surgery corneas included pentacam analyzer, H&amp;E staining and optical coherence tomography (OCT), transmission electron microscopy (TEM), raman spectroscopy and uniaxial tensile tests. Later, tandem mass tag-labeled proteomics and multiply statistic analysis were performed on post-PRK75 corneas. Western blot was used to validate protein expression. Herein, we found that tapered corneal thinning in post-PRK corneas predisposed to corneal ectasia. Greater ablation depth increased ectasia risk. PRK75 (ablation of 75% of corneal thickness using PRK mode) emerged as the optimal modeling approach, evidenced by significant and sustained corneal ectasia for 4 weeks. The 4-week post-PRK75 corneas were evaluated by changes in stromal cell microstructure, basement membrane, collagen lamellae, collagen covalent bonds and decreased corneal biomechanical strength. Additionally, PRK75 surgery induced 109 differentially expressed proteins (DEPs), with 51 previously linked to human corneal ectasia. The statistic analysis demonstrated the dysregulation of immue response was involved in the post-PRK75 corneas, and identified nine core proteins involved in corneal ectasia, including SERPINH1, ALDH1A1, MMP10, A2M, GSTM3, CD44, CLU, C3, and ITGB2. Therefore, we concluded that PRK75 was a novel and reliable modeling method for corneal ectasia, resemble human corneal ectasia. The intrinsic structural remodeling and molecular alteration in post-PRK75 corneas could shed lights on understanding the mechanism of biomechanical cues in corneal ectasia in the future.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110248"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037713","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}

{"title":"Topical application of amniotic membrane extract at a clinically correlated dose is effective in limiting complications in an experimental ocular alkaline burn model","authors":"Muhammed Dara Tas ,&nbsp;Mehmet Gurdal ,&nbsp;Meltem Kocamanoglu ,&nbsp;Ilayda Korkmaz ,&nbsp;Mesut Arici ,&nbsp;Banu Yaman ,&nbsp;Melis Palamar ,&nbsp;Nuri Yildirim ,&nbsp;Ali Çalışır ,&nbsp;Eda Seçil Gönen ,&nbsp;Ilgin Timarci Becerik ,&nbsp;Ozlem Barut Selver","doi":"10.1016/j.exer.2025.110259","DOIUrl":"10.1016/j.exer.2025.110259","url":null,"abstract":"<div><div>The purpose of this study is to investigate the clinical and histopathological effectiveness of topical amniotic membrane extract (AME) applied at a clinically relevant dose in an experimental corneal alkaline burn model and to compare the results with amniotic membrane transplantation (AMT) as one of the most frequently used biologically based treatment options. To create an alkaline burn model, NaOH-impregnated filter paper was applied to all rabbits for 30 s. Rabbits were divided into 3 groups: Group 1 (n = 6): AME eye drop; Group 2 (n = 6): AMT; Group 3 (n = 4): control group. AME eye drops were applied as 1 drop 4 times a day for 28 days. Clinical findings including corneal opacity, corneal vascularization, limbal stem cell deficiency (LSCD) was evaluated and graded in accordance with the updated literature. On day 28, corneas were histopathologically examined under the light microscope. Stromal inflammation, stromal fibrosis, intraepithelial edema, and corneal vascularization were scored in each group. When the groups were compared clinically, corneal opacity was significantly (p = 0.009) lower in the AME group. While lower LSCD grades were observed in the AME group, this difference was not significant (p &gt; 0.05). Histopathologically; in the AME group, stromal inflammatory cell inflammation, corneal vascularization, intraepithelial edema, stromal fibrosis, and metaplastic epithelial layer thickness were significantly (p = 0.004; p = 0.022; p = 0.008; p = 0.002; p = 0.002, respectively) lower than the other groups.In this study, it was shown that AME eye drops were clinically and histopathologically more successful in providing corneal healing than the AMT and control groups in the ocular alkaline burn model. These findings are valuable as they show that AME eye drops may be an easy-to-apply biologically based treatment alternative to AMT in chemical burns.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110259"},"PeriodicalIF":3.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074287","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}

{"title":"Disruption of circadian intraocular pressure fluctuations in mice by the Lyst beige-J mutation","authors":"Colleen M. McDowell ,&nbsp;Laura M. Dutca ,&nbsp;Stewart Thompson ,&nbsp;Megan Riker ,&nbsp;Adam Hedberg-Buenz ,&nbsp;Kacie J. Meyer ,&nbsp;Michael G. Anderson","doi":"10.1016/j.exer.2025.110266","DOIUrl":"10.1016/j.exer.2025.110266","url":null,"abstract":"<div><div>Intraocular pressure (IOP) follows a circadian rhythm. In both humans and mice, IOP is normally slightly elevated at night during the dark phase of the light cycle. In studying a strain of mice for possible indices of glaucoma, we incidentally discovered that C57BL/6J mice homozygous for the <em>beige-J</em> mutation of the <em>Lyst</em> gene lack a circadian fluctuation in IOP. Instead of having an elevated dark phase IOP, homozygotes exhibit a uniform IOP characteristic for light period values of C57BL/6J mice. The <em>beige-J</em> mutation results from deletion of a single isoleucine amino acid in the LYST WD40 motif likely to influence protein-protein interactions. Based on the literature, we hypothesized that CSNK2B (casein kinase 2, beta polypeptide) might be a relevant interacting protein, which we confirmed with a pulldown assay as a binding partner of wild-type, but not <em>beige-J</em> encoding, LYST protein. Treating wild-type mice with 4,5,6,7-tetrabromobenzotriazole (TBB), a casein kinase 2 inhibitor, recapitulated the <em>beige-J</em> mutant phenotype in preventing a rise in IOP during the dark period. Together, these results identify <em>Lyst beige-J</em> mice as a new strain for studying circadian IOP regulation and point to casein kinase 2 as a key molecule of interest.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110266"},"PeriodicalIF":3.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079170","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}

{"title":"Corneal stromal cells from patients with keratoconus exhibit alterations in the ESCRT-dependent machinery responsible for multivesicular body formation","authors":"Noelia Blanco-Agudín ,&nbsp;Suhui Ye ,&nbsp;Ignacio Alcalde ,&nbsp;María Daniela Corte-Torres ,&nbsp;David Galarreta ,&nbsp;Manuel Caro-Magdaleno ,&nbsp;Iván Fernández-Vega ,&nbsp;Luis Fernández-Vega Cueto ,&nbsp;Jesús Merayo-Lloves ,&nbsp;Luis M. Quirós","doi":"10.1016/j.exer.2025.110260","DOIUrl":"10.1016/j.exer.2025.110260","url":null,"abstract":"<div><div>Previous studies have reported that exosomes produced by corneal stromal cells from keratoconus patients exhibit a molecular content distinct from those produced by cells from healthy donors.</div><div>This study investigates differences in the expression of ESCRT components, regarded as the most critical mechanism in exosome biogenesis. The study included analysis of transcription levels of system-encoding genes using qRT-PCR reactions, as well as semiquantitative protein determination through immunocytochemistry.</div><div>Of the 34 molecules analyzed, mRNA downregulation was observed in 8 in pathological cells. In keratoconus, genes encoding STAM2 from the ESCRT-0 complex and VPS37A, VPS37C, VPS37D and UBAP1 from the ESCRT-I complex were found to be underexpressed, although VPS37D could not be confirmed at the protein level. Additionally, two other expression alterations affected the ESCRT-III complex, involving the core protein CHMP4C and the regulatory protein CHMP1B. Finally, deregulation of the ubiquitin-specific peptidase UBPY was observed.</div><div>Most changes identified in this study affected specific isoforms, which could suggest functional diversification and differences in cargo recognition in the context of pathology. Altogether, these findings suggest that the previously reported alteration in the molecular content of exosomes produced by stromal cells in keratoconus may be, at least partially, due to disruptions in the exosome synthesis machinery.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110260"},"PeriodicalIF":3.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074283","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}

{"title":"Retinal Phenotypes and Single-cell Sequencing Analysis of Ush2a Knockout Mice.","authors":"Yudie Ning, Longhao Kuang, Tao Huang, JunFeng Lv, Xiaohe Yan","doi":"10.1016/j.exer.2025.110247","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110247","url":null,"abstract":"<p><p>Usher syndrome is a rare autosomal recessive genetic disorder that primarily affects both vision and hearing, manifesting as sensorineural hearing loss and progressive vision loss caused by retinitis pigmentosa. The pathogenesis of retinal degeneration in Usher syndrome is still largely unknown. In this study, a novel Ush2a knockout mouse model was successfully constructed using CRISPR/Cas9 technology. Auditory brainstem response tests, electroretinography, HE staining and retinal single-cell RNA sequencing were performed in Ush2a knockout and wild-type mice. Initial phenotypic observations of Ush2a knockout mice revealed auditory functional impairment in Ush2a knockout mice at 6 months, but no apparent morphological and electrophysiological phenotypes in the retina were found at 20 months. Single-cell RNA sequencing was performed to understand the expression profiles of various cell types in the retina of Ush2a knockout mice, and an initial single-cell regulatory map was constructed. Our study initially elucidated the possible mechanisms of Ush2a-related molecules and the potential regulatory programs of cells during development.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110247"},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064720","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}

{"title":"Intravitreal AAV-IKV mediated delivery of decorin inhibits choroidal neovascularization, fibrosis, inflammation and elevates autophagy","authors":"Manish Mishra,&nbsp;Siobhan M. Cashman,&nbsp;Rajendra Kumar-Singh","doi":"10.1016/j.exer.2025.110258","DOIUrl":"10.1016/j.exer.2025.110258","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. The exudative or wet form of AMD is caused by choroidal neovascularization (CNV) and subsequently a macular edema. Wet AMD can be effectively treated with anti-vascular endothelial growth factor (VEGF) therapies. However, despite treatment, more than half of patients continue to lose vision due to a lack of compliance with frequent intravitreal injections, failure to adequately respond to anti-VEGF therapy and emergence of fibrotic scars underneath the retina. In this study we investigated the use of our retinal penetrating AAV for delivery of human decorin (AAV-IKV-Decorin) in a murine model of laser induced CNV. Our results indicate that following a single intravitreal injection, decorin is highly expressed in the outer retina of AAV-IKV-Decorin injected mice and such mice exhibit significantly less neovascularization in laser induced CNV relative to mice injected with an AAV-IKV-Aflibercept, an AAV expressing an anti-VEGF. AAV-IKV-Decorin also significantly inhibited fibrosis, reduced inflammatory markers and increased autophagy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110258"},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064718","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}

{"title":"Single-cell transcriptomic profiling of rat iridocorneal angle at perinatal stages: Revisiting the development of periocular mesenchyme","authors":"Yunsheng Qiao ,&nbsp;Chen Tan ,&nbsp;Junyi Lai ,&nbsp;Jihong Wu ,&nbsp;Xinghuai Sun ,&nbsp;Junyi Chen","doi":"10.1016/j.exer.2025.110249","DOIUrl":"10.1016/j.exer.2025.110249","url":null,"abstract":"<div><div>The periocular mesenchyme (POM) gives rise to key structures in the ocular anterior segment, and its malformation leads to anterior segment dysgenesis (ASD) with iridocorneal angle (ICA) abnormalities. However, the transcriptional profile of the POM and the regulatory mechanisms governing cell-fate decision during anterior eye and ICA development remain poorly understood. In this study, we performed a comprehensive time-series analysis by sequencing rat anterior ocular samples collected at five consecutive perinatal stages: embryonic days 16.5 and 18.5, the day of birth, and postnatal days 4 and 8, at the single-cell level and validated a portion of <em>in silico</em> findings with immunostaining. High-quality transcriptomes were obtained from 59,416 cells with diverse embryonic origins. A prominent transcriptional shift was observed in POM cells, coinciding with anatomical alterations around the ICA shortly after birth. We illustrated the molecular signatures of five POM subclusters while tracing their developmental trajectories. Additionally, we identified key driver genes, as well as cell type-specific and stage-wise gene modules underlying lineage specification. Furthermore, the switch of regulon network and cellular crosstalk associated with POM maturation were unveiled. Lastly, we mapped ASD-relevant genes to this single-cell atlas, revealing distinct expression patterns. Collectively, this study provides a transcriptomic blueprint for understanding normal POM and ICA development, as well as a valuable reference for future research into ASD pathogenesis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110249"},"PeriodicalIF":3.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037716","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}

{"title":"Priming and release of cytokine IL-1β in microglial cells from the retina","authors":"Keith E. Campagno ,&nbsp;Wennan Lu ,&nbsp;Puttipong Sripinun ,&nbsp;Farraj Albalawi ,&nbsp;Aurora Cenaj ,&nbsp;Claire H. Mitchell","doi":"10.1016/j.exer.2025.110246","DOIUrl":"10.1016/j.exer.2025.110246","url":null,"abstract":"<div><div>The P2X7 receptor (P2X7R) for extracellular ATP is implicated in several forms of retinal degeneration, including diabetic retinopathy, age-related macular degeneration, and glaucoma. P2X7R stimulation can trigger release of master cytokine IL-1β from microglia in the brain and from macrophages, but evidence of release from retinal microglia is indirect. Isolated mouse and rat retinal microglia, and wholemounts from Cx3CR1^+/GFP mice, were examined to determine if ATP induced IL-1β release directly from retinal microglial cells and if it also primed expression of IL-1β on an mRNA and protein level. Isolated retinal microglia were ramified and expressed low levels of polarization markers unless provoked. Over 90% of isolated microglial cells expressed P2X7R, with cytoplasmic Ca²⁺ elevation following receptor stimulation. ATP induced a dose-dependent release of IL-1β from primed microglial cells that was blocked by P2X7R antagonist A839977 and emulated by agonist BzATP. P2X7R stimulation also primed <em>Il1b</em> mRNA in isolated microglia cells. BzATP increased IL-1β immunostaining and GFP fluorescence throughout lamina of retinal wholemounts from CX3CR1^+/GFP mice. Some of the IL-1β and GFP signals colocalized, particularly in the outer retina, and in projections extending distally through photoreceptor layers. The inner retina had more microglia without IL-1β, and more IL-1β staining without microglia. Substantial IL-1β release was also detected from rat retinal microglial cells, but not optic nerve head astrocytes. In summary, this study implicates microglial cells as a key source of released IL-1β when levels of extracellular ATP are increased following retinal damage, and suggest a greater participation in the outer retina.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110246"},"PeriodicalIF":3.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028403","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}

{"title":"SREBF1 facilitates pathological retinal neovascularization by reprogramming the fatty acid metabolism of endothelial cells","authors":"Hangjia Zuo ,&nbsp;Xianyang Liu ,&nbsp;Yakun Wang ,&nbsp;Huannan Ding ,&nbsp;Wenjuan Wan ,&nbsp;Shijie Zheng ,&nbsp;Shengping Hou ,&nbsp;Ke Hu","doi":"10.1016/j.exer.2025.110239","DOIUrl":"10.1016/j.exer.2025.110239","url":null,"abstract":"<div><div>Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder that critically affects the visual development of premature infants, potentially leading to irreversible vision loss or even blindness. Despite its significance, the underlying mechanisms of this disease remain insufficiently understood. In this study, we utilized the oxygen-induced retinopathy (OIR) mouse model and conducted endothelial functional assays to explore the role of Sterol Regulatory Element-Binding Protein 1 (SREBF1) in ROP pathogenesis. SREBF1 expression levels, along with its downstream targets, were investigated through Western blotting, RT-qPCR, and immunofluorescence staining techniques. Furthermore, Co-Immunoprecipitation (Co-IP) was employed to examine the molecular mechanisms involved. Our results demonstrated a significant increase in SREBF1 expression in both the OIR mouse model and hypoxic primary human retinal microvascular endothelial cells (HRMECs). Interventions conducted both in vivo and in vitro showed notable efficacy in reducing pathological neovascularization. Importantly, we discovered that SREBF1 plays a key role in modulating lipid metabolism in HRMECs by regulating the expression of ACC1 and FASN, leading to cellular reprogramming. This reprogramming influences HRMEC proliferation, migration, and tube formation through the HIF-1α/TGF-β signaling pathway, ultimately contributing to pathological retinal neovascularization. These findings provide new insights into the role of SREBF1 in angiogenesis within the context of ROP, offering potential therapeutic targets for the management and treatment of this disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110239"},"PeriodicalIF":3.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970315","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}