Pub Date : 2025-12-18DOI: 10.1016/j.exer.2025.110811
Tianyu Cheng , Pengfei Li , Jiancen Tang , Hongping Cui , Jierui Jia , Lu Wang , Qian Li
DNA oxidative damage of lens epithelium cells (LECs) has been proved to be significantly related to age-related cataract (ARC). DCLRE1A, as a member of the DNA interstrand cross-links pathway, can repair damaged DNA. However, DCLRE1A has not been addressed in maintaining mitochondrial healthy. Our findings demonstrated that DCLRE1A alleviated mtDNA oxidative damage and mitochondrial dysfunction. Besides, the E3 ubiquitin ligase SYVN1 interacts with DCLRE1A and promotes its ubiquitination and degradation. Furthermore, SYVN1 knockdown exacerbated H2O2-induced lens opacity in both ex-vitro rat lenses and ARC mouse. Together, these results underscore the pivotal role of DCLRE1A ubiquitination in modulating mitochondrial homeostasis, offering novel insights into ARC pathogenesis. The E3 ubiquitin ligase SYVN1, related to DNA damage repair, offers a promising avenue for treating cataracts with antioxidative.
{"title":"DCLRE1 downregulated by SYVN1-mediated ubiquitination and degradation, weakening mitochondrial homeostasis protection in ARC formation","authors":"Tianyu Cheng , Pengfei Li , Jiancen Tang , Hongping Cui , Jierui Jia , Lu Wang , Qian Li","doi":"10.1016/j.exer.2025.110811","DOIUrl":"10.1016/j.exer.2025.110811","url":null,"abstract":"<div><div>DNA oxidative damage of lens epithelium cells (LECs) has been proved to be significantly related to age-related cataract (ARC). DCLRE1A, as a member of the DNA interstrand cross-links pathway, can repair damaged DNA. However, DCLRE1A has not been addressed in maintaining mitochondrial healthy. Our findings demonstrated that DCLRE1A alleviated mtDNA oxidative damage and mitochondrial dysfunction. Besides, the E3 ubiquitin ligase SYVN1 interacts with DCLRE1A and promotes its ubiquitination and degradation. Furthermore, SYVN1 knockdown exacerbated H<sub>2</sub>O<sub>2</sub>-induced lens opacity in both ex-vitro rat lenses and ARC mouse. Together, these results underscore the pivotal role of DCLRE1A ubiquitination in modulating mitochondrial homeostasis, offering novel insights into ARC pathogenesis. The E3 ubiquitin ligase SYVN1, related to DNA damage repair, offers a promising avenue for treating cataracts with antioxidative.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110811"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800061","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":"Comment on “Synergistic neuroprotective effects of the ROCK inhibitor Y27632 and atorvastatin in optineurin-E50K-mutant mice through inhibition of scleral fibroblast transdifferentiation”","authors":"Bhumesh Tyagi , Leelabati Toppo , Aishwarya Biradar","doi":"10.1016/j.exer.2025.110818","DOIUrl":"10.1016/j.exer.2025.110818","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110818"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796622","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}
Pub Date : 2025-12-18DOI: 10.1016/j.exer.2025.110816
Katherine Borner , Ze Yu , Chao Xing , W. Matthew Petroll
Following injury or surgery, quiescent stromal keratocytes can transition into fibroblasts or myofibroblasts leading to either transient or protracted corneal haze. In this study, we investigate the transcriptional changes associated with non-fibrotic wound healing using a transcorneal freeze injury (FI) in the rabbit, which induces full-thickness stromal cell loss without inducing keratocyte-myofibroblast transformation.
In control corneas, scRNA-seq revealed multiple clusters expressing markers associated with keratocyte identity (e.g. KERA, LUM, DCN, and ALDH1A1), suggesting heterogeneity in stromal keratocytes in the uninjured stroma. On day 7 after FI, in vivo imaging revealed elongated cells with increased backscatter, consistent with fibroblast migration into the wounded region. Using scRNA-seq, two additional clusters expressing fibroblast markers were also identified. These clusters retained many markers consistent with keratocyte identity, and trajectory analysis demonstrated a continuous progression from quiescent keratocytes to fibroblasts. Both fibroblast clusters had elevated expression genes encoding tenascin C (TNC), claudin 5 (CLDN5), developmental proteoglycans (e.g., BGN, ASPN, VCAN), and cytoskeletal genes (MYL9, MYH10, CDH11), but did not express markers of myofibroblast transformation. Together these genes suggest a mechanically active but non-fibrotic phenotype. One of the two fibroblast clusters also expressed genes related to cell proliferation. By day 28, fibroblastic gene expression was reduced, consistent with resolution of wound healing.
These findings define the transcriptional dynamics of intrastromal cell migration following FI and reveal a transient fibroblastic state that supports wound repopulation without fibrosis. Understanding this non-fibrotic repair mechanism could inform strategies to prevent scarring following corneal surgery or injury.
{"title":"Single cell RNA-seq characterization of non-fibrotic stromal wound repopulation in the rabbit","authors":"Katherine Borner , Ze Yu , Chao Xing , W. Matthew Petroll","doi":"10.1016/j.exer.2025.110816","DOIUrl":"10.1016/j.exer.2025.110816","url":null,"abstract":"<div><div>Following injury or surgery, quiescent stromal keratocytes can transition into fibroblasts or myofibroblasts leading to either transient or protracted corneal haze. In this study, we investigate the transcriptional changes associated with non-fibrotic wound healing using a transcorneal freeze injury (FI) in the rabbit, which induces full-thickness stromal cell loss without inducing keratocyte-myofibroblast transformation.</div><div>In control corneas, scRNA-seq revealed multiple clusters expressing markers associated with keratocyte identity (e.g. KERA, LUM, DCN, and ALDH1A1), suggesting heterogeneity in stromal keratocytes in the uninjured stroma. On day 7 after FI, <em>in vivo</em> imaging revealed elongated cells with increased backscatter, consistent with fibroblast migration into the wounded region. Using scRNA-seq, two additional clusters expressing fibroblast markers were also identified. These clusters retained many markers consistent with keratocyte identity, and trajectory analysis demonstrated a continuous progression from quiescent keratocytes to fibroblasts. Both fibroblast clusters had elevated expression genes encoding tenascin C (TNC), claudin 5 (CLDN5), developmental proteoglycans (e.g., BGN, ASPN, VCAN), and cytoskeletal genes (MYL9, MYH10, CDH11), but did not express markers of myofibroblast transformation. Together these genes suggest a mechanically active but non-fibrotic phenotype. One of the two fibroblast clusters also expressed genes related to cell proliferation. By day 28, fibroblastic gene expression was reduced, consistent with resolution of wound healing.</div><div>These findings define the transcriptional dynamics of intrastromal cell migration following FI and reveal a transient fibroblastic state that supports wound repopulation without fibrosis. Understanding this non-fibrotic repair mechanism could inform strategies to prevent scarring following corneal surgery or injury.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110816"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800231","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}
Cardiovascular disease (CVD) remains a major global burden, and retinal microvascular imaging offers a noninvasive means to capture systemic microvascular status. Evidence from prospective cohorts shows that arteriolar narrowing and venular widening predict incident coronary heart disease, with pooled adjusted hazard ratios approximately 1.20 (95 % CI 1.13–1.27). Network-level metrics, including reduced fractal dimension and increased tortuosity, further reflect microvascular remodeling and have been associated with higher risks of CVD and heart failure. In diabetes, both the presence and severity of diabetic retinopathy, as well as an AI-derived retinal age gap, correlate with elevated rates of cardiovascular events, kidney disease progression, and all-cause mortality. OCTA studies demonstrate that vessel-density loss and foveal avascular zone alterations occur in hypertension, coronary disease, heart failure, and stroke; longitudinal data indicate that sustained reductions in vessel density of several percentage points are associated with increased major adverse cardiovascular events. AI models trained on retinal images, particularly when integrated with clinical variables, achieve discrimination comparable to or exceeding traditional risk scores, with reported AUC improvements of up to ∼0.07. Despite these advances, most studies remain cross-sectional, OCTA metrics vary significantly across devices, and AI models often lack external validation and explicit assessment of incremental predictive value. Priority areas include prospective multi-ethnic cohorts with standardized imaging protocols, harmonized OCTA acquisition and analysis, and interpretable, externally validated AI systems capable of demonstrating measurable clinical benefit before retinal biomarkers can be incorporated into routine cardiovascular risk stratification.
心血管疾病（CVD）仍然是一个主要的全球负担，视网膜微血管成像提供了一种非侵入性手段来捕获系统微血管状态。来自前瞻性队列的证据显示，小动脉狭窄和静脉扩大预测冠心病的发生，合并校正风险比约为1.20 （95% CI 1.13-1.27）。网络级指标，包括分形维数降低和弯曲度增加，进一步反映微血管重塑，并与心血管疾病和心力衰竭的高风险相关。在糖尿病中，糖尿病视网膜病变的存在和严重程度，以及人工智能引发的视网膜年龄差距，都与心血管事件、肾脏疾病进展和全因死亡率升高相关。OCTA研究表明，高血压、冠心病、心力衰竭和中风患者会出现血管密度下降和中央凹无血管区改变；纵向数据表明，血管密度持续降低几个百分点与主要不良心血管事件的增加有关。在视网膜图像上训练的人工智能模型，特别是当与临床变量相结合时，实现了与传统风险评分相当或超过传统风险评分的识别，据报道AUC改善高达0.07。尽管取得了这些进展，但大多数研究仍然是横向的，不同设备的OCTA指标差异很大，而且人工智能模型往往缺乏外部验证和对增量预测价值的明确评估。优先领域包括具有标准化成像方案的前瞻性多民族队列，协调的OCTA采集和分析，以及可解释的，外部验证的AI系统，能够在将视网膜生物标志物纳入常规心血管风险分层之前展示可测量的临床益处。
{"title":"Retinal microvascular biomarkers for cardiovascular risk stratification: Insights from OCTA and AI","authors":"Ting Wang, Hongyu Li, Chuyao Wang, Xiuyun Li, Aijun Deng, Xinwei Jiao","doi":"10.1016/j.exer.2025.110815","DOIUrl":"10.1016/j.exer.2025.110815","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) remains a major global burden, and retinal microvascular imaging offers a noninvasive means to capture systemic microvascular status. Evidence from prospective cohorts shows that arteriolar narrowing and venular widening predict incident coronary heart disease, with pooled adjusted hazard ratios approximately 1.20 (95 % CI 1.13–1.27). Network-level metrics, including reduced fractal dimension and increased tortuosity, further reflect microvascular remodeling and have been associated with higher risks of CVD and heart failure. In diabetes, both the presence and severity of diabetic retinopathy, as well as an AI-derived retinal age gap, correlate with elevated rates of cardiovascular events, kidney disease progression, and all-cause mortality. OCTA studies demonstrate that vessel-density loss and foveal avascular zone alterations occur in hypertension, coronary disease, heart failure, and stroke; longitudinal data indicate that sustained reductions in vessel density of several percentage points are associated with increased major adverse cardiovascular events. AI models trained on retinal images, particularly when integrated with clinical variables, achieve discrimination comparable to or exceeding traditional risk scores, with reported AUC improvements of up to ∼0.07. Despite these advances, most studies remain cross-sectional, OCTA metrics vary significantly across devices, and AI models often lack external validation and explicit assessment of incremental predictive value. Priority areas include prospective multi-ethnic cohorts with standardized imaging protocols, harmonized OCTA acquisition and analysis, and interpretable, externally validated AI systems capable of demonstrating measurable clinical benefit before retinal biomarkers can be incorporated into routine cardiovascular risk stratification.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110815"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796623","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}
Pub Date : 2025-12-18DOI: 10.1016/j.exer.2025.110813
Bin Li , Liping Yan
{"title":"Comment on “Synergistic neuroprotective effects of the ROCK inhibitor Y27632 and atorvastatin in optineurin-E50K-mutant mice through inhibition of scleral fibroblast transdifferentiation” by Zhu et al.","authors":"Bin Li , Liping Yan","doi":"10.1016/j.exer.2025.110813","DOIUrl":"10.1016/j.exer.2025.110813","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110813"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800140","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}
Pub Date : 2025-12-18DOI: 10.1016/j.exer.2025.110808
Iliya Sharifipanah , Zohreh Abdolmaleki , Mohammad Abarkar
Corneal wound healing poses a significant clinical challenge involving cell death, migration, proliferation, and extracellular matrix remodeling. This study explores the effects of alpha-lipoic acid (LA) and retinoic acid (RA) eye drops on re-epithelialization, inflammation, and angiogenesis in a rabbit model of corneal wound healing, focusing on ICAM-1 (Intercellular Adhesion Molecule-1) and MMP-9 (Matrix Metalloroteinase-9) pathways. After an ocular examination of twelve New Zealand rabbits, a vertical linear wound was induced under anesthesia and confirmed by fluorescein staining. They were divided into four groups: control (isotonic saline), LA 1 %, RA 0.05 %, and a combination of both (RA + LA), administered twice daily for seven days. Clinical parameters and histological evaluations using H&E staining were conducted. Gene expression levels of ICAM-1, MMP-9, PDGFRα (Platelet-Derived Growth Factor Receptor α), and TGF-β (Transforming Growth Factor β) were measured by real-time PCR, with keratocan analyzed through immunohistochemistry. All treatment groups demonstrated significantly improved corneal healing compared to the control, with the RA + LA group showing the best histological repair. Real-time PCR results revealed significantly higher gene expression levels in the combination group than in the control and RA groups, and keratocan expression was significantly elevated in all treatment groups. In conclusion, LA and RA eye drops effectively enhance corneal healing by reducing inflammation and promoting re-epithelialization and angiogenesis, with the combined treatment showing the most pronounced effects.
{"title":"Investigating the effect of alpha-lipoic acid and retinoic acid eye drops on re-epithelialization, inflammation, and angiogenesis in a rabbit model of corneal wound healing through ICAM-1 and MMP-9 pathways","authors":"Iliya Sharifipanah , Zohreh Abdolmaleki , Mohammad Abarkar","doi":"10.1016/j.exer.2025.110808","DOIUrl":"10.1016/j.exer.2025.110808","url":null,"abstract":"<div><div>Corneal wound healing poses a significant clinical challenge involving cell death, migration, proliferation, and extracellular matrix remodeling. This study explores the effects of alpha-lipoic acid (LA) and retinoic acid (RA) eye drops on re-epithelialization, inflammation, and angiogenesis in a rabbit model of corneal wound healing, focusing on ICAM-1 (Intercellular Adhesion Molecule-1) and MMP-9 (Matrix Metalloroteinase-9) pathways. After an ocular examination of twelve New Zealand rabbits, a vertical linear wound was induced under anesthesia and confirmed by fluorescein staining. They were divided into four groups: control (isotonic saline), LA 1 %, RA 0.05 %, and a combination of both (RA + LA), administered twice daily for seven days. Clinical parameters and histological evaluations using H&E staining were conducted. Gene expression levels of ICAM-1, MMP-9, PDGFRα (Platelet-Derived Growth Factor Receptor α), and TGF-β (Transforming Growth Factor β) were measured by real-time PCR, with keratocan analyzed through immunohistochemistry. All treatment groups demonstrated significantly improved corneal healing compared to the control, with the RA + LA group showing the best histological repair. Real-time PCR results revealed significantly higher gene expression levels in the combination group than in the control and RA groups, and keratocan expression was significantly elevated in all treatment groups. In conclusion, LA and RA eye drops effectively enhance corneal healing by reducing inflammation and promoting re-epithelialization and angiogenesis, with the combined treatment showing the most pronounced effects.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110808"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796627","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}
Pub Date : 2025-12-16DOI: 10.1016/j.exer.2025.110807
Antoni Vallbona-Garcia , James R. Tribble , Simon T. Gustavsson , Birke J. Benedikter , Patrick J. Lindsey , Carroll AB. Webers , Hubert JM. Smeets , Gauti Jóhannesson , Theo GMF. Gorgels , Pete A. Williams
In glaucoma, retinal ganglion cell degeneration has been linked to declining mitochondrial metabolic capacity. Nicotinamide (NAM) supplementation has emerged as a potential treatment for this. We assessed the effects of a 2-week NAM supplementation on blood buffy coat mitochondrial content (qPCR to assess mtDNA amount per cell) and the plasma metabolome (small-molecular-weight high-resolution mass spectrometry) in 90 glaucoma subjects from 3 different glaucoma subtypes (high tension glaucoma (HTG), normal tension glaucoma (NTG), and pseudoexfoliative glaucoma (PEXG), n = 30 per group), and 30 healthy controls with similar age and sex distribution. At baseline (pre-NAM), only ethylmalonic acid, a compound related to defects in β-oxidation and mitochondrial dysfunction, was found to be modestly increased in the 3 glaucoma subtypes in comparison to controls. All groups showed a similar metabolome response to treatment with a specific increase in NAM and related species (1-methylnicotinamide, 6-hydroxynicotinamide, N1-methyl-2-pyridone-5-carboxamide), increased 5-methylcytosine, and decreased 4-pyridoxic acid. Between groups, only sarcosine had a different response, with a small reduction in HTG and NTG post-treatment. NAM treatment resulted in a significant but slight within-group increase in blood mtDNA amount in controls and HTG (12 % and 17 %, respectively). This study suggests that NAM treatment leads to similar plasma metabolome changes between glaucoma groups and controls, which predominantly reflect increased NAM metabolites and intermediates, with minimal effects on the wider metabolome, and a modest increase in mtDNA amount in HTG and controls. As this was observed in a short-term accelerated dosing context, long-term and larger studies with additional timepoints and greater adjustment for systemic metabolic factors will be required to provide more information on the long-term effects of oral NAM supplementation.
{"title":"Short-term high-dose nicotinamide treatment across glaucoma subtypes reveals increased mtDNA content and minimal metabolomic change in blood","authors":"Antoni Vallbona-Garcia , James R. Tribble , Simon T. Gustavsson , Birke J. Benedikter , Patrick J. Lindsey , Carroll AB. Webers , Hubert JM. Smeets , Gauti Jóhannesson , Theo GMF. Gorgels , Pete A. Williams","doi":"10.1016/j.exer.2025.110807","DOIUrl":"10.1016/j.exer.2025.110807","url":null,"abstract":"<div><div>In glaucoma, retinal ganglion cell degeneration has been linked to declining mitochondrial metabolic capacity. Nicotinamide (NAM) supplementation has emerged as a potential treatment for this. We assessed the effects of a 2-week NAM supplementation on blood buffy coat mitochondrial content (qPCR to assess mtDNA amount per cell) and the plasma metabolome (small-molecular-weight high-resolution mass spectrometry) in 90 glaucoma subjects from 3 different glaucoma subtypes (high tension glaucoma (HTG), normal tension glaucoma (NTG), and pseudoexfoliative glaucoma (PEXG), n = 30 per group), and 30 healthy controls with similar age and sex distribution. At baseline (pre-NAM), only ethylmalonic acid, a compound related to defects in β-oxidation and mitochondrial dysfunction, was found to be modestly increased in the 3 glaucoma subtypes in comparison to controls. All groups showed a similar metabolome response to treatment with a specific increase in NAM and related species (1-methylnicotinamide, 6-hydroxynicotinamide, N1-methyl-2-pyridone-5-carboxamide), increased 5-methylcytosine, and decreased 4-pyridoxic acid. Between groups, only sarcosine had a different response, with a small reduction in HTG and NTG post-treatment. NAM treatment resulted in a significant but slight within-group increase in blood mtDNA amount in controls and HTG (12 % and 17 %, respectively). This study suggests that NAM treatment leads to similar plasma metabolome changes between glaucoma groups and controls, which predominantly reflect increased NAM metabolites and intermediates, with minimal effects on the wider metabolome, and a modest increase in mtDNA amount in HTG and controls. As this was observed in a short-term accelerated dosing context, long-term and larger studies with additional timepoints and greater adjustment for systemic metabolic factors will be required to provide more information on the long-term effects of oral NAM supplementation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110807"},"PeriodicalIF":2.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780369","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}
Pub Date : 2025-12-10DOI: 10.1016/j.exer.2025.110805
Xiao Wang , Jiaxin Chen , Xi Chen , Yuke Huang , Yan Li , Jin Qiu , Haoting Chen , Qingqing Mu , Jiejie Zhuang , Yiqi Luo , Taiwei Chen , Na Yu , Pei Chen , Ying Yang , Lai Wei , Jing Zhuang
Corneal epithelial regeneration is critical for restoring ocular surface function after injury. This study investigated the therapeutic potential and molecular mechanism of honokiol (HNK) in promoting corneal epithelial repair. Using a murine corneal epithelial debridement model, we observed that HNK accelerated wound healing and upregulated KRT12 and Ki67 expression in injured corneas. In vitro, HNK significantly enhanced proliferation and migration of human corneal epithelial cells (HCE-T), as demonstrated by CCK-8 and scratch assays. Bulk RNA sequencing identified differentially expressed genes following HNK treatment, and subsequent bioinformatics analysis highlighted the mitochondrial enzyme 3-hydroxymethylglutaryl CoA synthetase 2 (HMGCS2) as a key mediator. HMGCS2, the mitochondrial isoform of 3-hydroxy-3-methylglutaryl-CoA synthase, serves as a critical regulatory node in lipid-derived ATP production and ketogenesis. Gene interference and mitochondrial activity assays confirmed that HNK promotes corneal epithelial repair by targeting HMGCS2 and enhancing mitochondrial function. These findings suggest that HNK facilitates corneal wound healing through a mitochondria-dependent mechanism, offering a potential therapeutic strategy for ocular surface regeneration.
{"title":"Honokiol (HNK) accelerates corneal epithelial wound healing by promoting HMGCS2-mediated mitochondrial metabolic homeostasis","authors":"Xiao Wang , Jiaxin Chen , Xi Chen , Yuke Huang , Yan Li , Jin Qiu , Haoting Chen , Qingqing Mu , Jiejie Zhuang , Yiqi Luo , Taiwei Chen , Na Yu , Pei Chen , Ying Yang , Lai Wei , Jing Zhuang","doi":"10.1016/j.exer.2025.110805","DOIUrl":"10.1016/j.exer.2025.110805","url":null,"abstract":"<div><div>Corneal epithelial regeneration is critical for restoring ocular surface function after injury. This study investigated the therapeutic potential and molecular mechanism of honokiol (HNK) in promoting corneal epithelial repair. Using a murine corneal epithelial debridement model, we observed that HNK accelerated wound healing and upregulated KRT12 and Ki67 expression in injured corneas. In vitro, HNK significantly enhanced proliferation and migration of human corneal epithelial cells (HCE-T), as demonstrated by CCK-8 and scratch assays. Bulk RNA sequencing identified differentially expressed genes following HNK treatment, and subsequent bioinformatics analysis highlighted the mitochondrial enzyme 3-hydroxymethylglutaryl CoA synthetase 2 (HMGCS2) as a key mediator. HMGCS2, the mitochondrial isoform of 3-hydroxy-3-methylglutaryl-CoA synthase, serves as a critical regulatory node in lipid-derived ATP production and ketogenesis. Gene interference and mitochondrial activity assays confirmed that HNK promotes corneal epithelial repair by targeting HMGCS2 and enhancing mitochondrial function. These findings suggest that HNK facilitates corneal wound healing through a mitochondria-dependent mechanism, offering a potential therapeutic strategy for ocular surface regeneration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110805"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741718","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}
Pub Date : 2025-12-09DOI: 10.1016/j.exer.2025.110804
Laurel C. Chandler , Apolonia Gardner , Constance L. Cepko
Retinitis pigmentosa is an inherited retinal disease caused by thousands of mutations in over 100 different genes. The most widely used mouse model for retinitis pigmentosa has the retinal degeneration 1 (rd1) mutation in the Pde6b gene, which elicits rapid retinal degeneration and vision loss. A major limitation of these models is that these rd1 strains are not congenic, which prevents the use of appropriate controls. Furthermore, many strains have mutations in other genes which introduces genetic variability and may confound results. To address this issue, we backcrossed the rd1 allele from FVB mice onto a C57BL/6J genetic background over many generations, producing a C57BL/6J.Pde6brd1 strain that was confirmed to be congenic to C57BL/6J mice. We show that this strain recapitulates the electroretinogram and optomotor results expected for mouse strains containing the rd1 mutation. Examination of retinal structure in cross sections of eyes isolated from C57BL/6J.Pde6brd1 mice show a degree of thinning of the outer nuclear layer expected for a rd1 mutation, resulting in nearly complete loss of the outer nuclear layer by postnatal day 35. We anticipate that this C57BL/6J.Pde6brd1 strain could become an asset for the field of retinitis pigmentosa research.
{"title":"A congenic C57BL/6J rd1 mouse model for retinal degeneration research","authors":"Laurel C. Chandler , Apolonia Gardner , Constance L. Cepko","doi":"10.1016/j.exer.2025.110804","DOIUrl":"10.1016/j.exer.2025.110804","url":null,"abstract":"<div><div>Retinitis pigmentosa is an inherited retinal disease caused by thousands of mutations in over 100 different genes. The most widely used mouse model for retinitis pigmentosa has the retinal degeneration 1 (<em>rd1</em>) mutation in the <em>Pde6b</em> gene, which elicits rapid retinal degeneration and vision loss. A major limitation of these models is that these <em>rd1</em> strains are not congenic, which prevents the use of appropriate controls. Furthermore, many strains have mutations in other genes which introduces genetic variability and may confound results. To address this issue, we backcrossed the <em>rd1</em> allele from FVB mice onto a C57BL/6J genetic background over many generations, producing a C57BL/6J.<em>Pde6b</em><sup><em>rd1</em></sup> strain that was confirmed to be congenic to C57BL/6J mice. We show that this strain recapitulates the electroretinogram and optomotor results expected for mouse strains containing the <em>rd1</em> mutation. Examination of retinal structure in cross sections of eyes isolated from C57BL/6J.<em>Pde6b</em><sup><em>rd1</em></sup> mice show a degree of thinning of the outer nuclear layer expected for a <em>rd1</em> mutation, resulting in nearly complete loss of the outer nuclear layer by postnatal day 35. We anticipate that this C57BL/6J.<em>Pde6b</em><sup><em>rd1</em></sup> strain could become an asset for the field of retinitis pigmentosa research.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110804"},"PeriodicalIF":2.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741732","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}
Pub Date : 2025-12-09DOI: 10.1016/j.exer.2025.110802
Yuyan Ren , Huazhi Zhang , Qingping Lan , Jingwen Tang , Yilan Li , Ziying Wang , Yapeng Wang
While diabetic retinopathy (DR) is the primary cause of vision impairment and blindness in people with diabetes, current treatments fail to target early pathogenic mechanisms to halt disease progression. The development of DR involves complex cellular stress responses associated with metabolic dysregulation. Recent studies have highlighted the critical functions of autophagy, particularly mitophagy, in DR and how it contributes to the malfunction of the retinal neurovascular unit (NVU) and disease progression. Emerging insights have elucidated the interplay between autophagy, ER stress, and regulatory genes such as DRAM2, with pivotal roles for mitophagy-related pathways, including PINK1/Parkin and BNIP3/NIX-FUNDC1. This review systematically organizes and analyzes recent advances in research on how autophagy and mitophagy regulate ER stress, mitochondrial homeostasis, and the function of diverse NVU cell types. We present evidence that dysregulation of these processes compromises NVU integrity and accelerates DR progression. By clarifying the molecular links between autophagy, mitophagy, and NVU dysfunction, this review offers new insights for developing precision interventions and innovative therapies for early intervention of DR.
{"title":"Autophagy and mitophagy in diabetic retinopathy: The effects and mechanism of action on the neurovascular unit","authors":"Yuyan Ren , Huazhi Zhang , Qingping Lan , Jingwen Tang , Yilan Li , Ziying Wang , Yapeng Wang","doi":"10.1016/j.exer.2025.110802","DOIUrl":"10.1016/j.exer.2025.110802","url":null,"abstract":"<div><div>While diabetic retinopathy (DR) is the primary cause of vision impairment and blindness in people with diabetes, current treatments fail to target early pathogenic mechanisms to halt disease progression. The development of DR involves complex cellular stress responses associated with metabolic dysregulation. Recent studies have highlighted the critical functions of autophagy, particularly mitophagy, in DR and how it contributes to the malfunction of the retinal neurovascular unit (NVU) and disease progression. Emerging insights have elucidated the interplay between autophagy, ER stress, and regulatory genes such as DRAM2, with pivotal roles for mitophagy-related pathways, including PINK1/Parkin and BNIP3/NIX-FUNDC1. This review systematically organizes and analyzes recent advances in research on how autophagy and mitophagy regulate ER stress, mitochondrial homeostasis, and the function of diverse NVU cell types. We present evidence that dysregulation of these processes compromises NVU integrity and accelerates DR progression. By clarifying the molecular links between autophagy, mitophagy, and NVU dysfunction, this review offers new insights for developing precision interventions and innovative therapies for early intervention of DR.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"263 ","pages":"Article 110802"},"PeriodicalIF":2.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741691","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}
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