Experimental eye research最新文献

{"title":"Association between gut microbiota dysbiosis and age-related macular degeneration progression: A bioinformatics approach","authors":"Jianxiong Yu ,&nbsp;Jing Yuan","doi":"10.1016/j.exer.2025.110596","DOIUrl":"10.1016/j.exer.2025.110596","url":null,"abstract":"<div><div>Gut microbiota dysbiosis has been linked to the progression of age-related macular degeneration, though the underlying molecular mechanisms remain unclear. This study is the first to systematically link gutMGene-derived genes to AMD pathogenesis using a multi-algorithm machine learning approach. Using the gutMGene database, we identified gut microbiota-related genes and analyzed the GSE29801 dataset for differential expression. Our enrichment analysis revealed unique insights into the involvement of gut microbiota-related genes in inflammatory, immune response, and metabolic pathways in age-related macular degeneration. Machine learning algorithms (LASSO, Random Forest, XGBoost) identified five consistent biomarker genes: <em>CXCL10</em>, <em>FADS3</em>, <em>GHRL</em>, <em>APOE</em>, and <em>VEGFA</em>. A nomogram was developed to predict AMD risk, showing moderate-to-high predictive accuracy with area under the curve of 0.719 (GSE29801) and 0.933 (GSE99248). Gene set variation analysis indicated upregulation of inflammatory and immune pathways and downregulation of lipid metabolism pathways in age-related macular degeneration. Single-gene set enrichment analysis further underscored the roles of diagnostic genes in immune response and metabolic regulation. This study contributes novel evidence that gut microbiota dysbiosis influences AMD progression through systemic inflammatory and metabolic pathways, and highlights potential therapeutic targets.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110596"},"PeriodicalIF":2.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948126","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":"Nitrogen mustard causes progressive tissue injury, severe DNA damage, and necroptosis in the cornea","authors":"Nan Gao,&nbsp;Fu-shin Yu","doi":"10.1016/j.exer.2025.110581","DOIUrl":"10.1016/j.exer.2025.110581","url":null,"abstract":"<div><div>The eye is sensitive and vulnerable to vesicants such as sulfur and nitrogen mustard (NM). To assess the adverse effects of NM exposure on the ocular surface, we used porcine and rat corneas and NM-wetted filtrate paper disks to assess NM's ex vivo and in vivo effects on corneal health. In cultured porcine corneas (N = 5), 5 mg/ml NM caused exposure time-dependent damage, which progressed from 1 to 2 days post-NM exposure (dpe), with increased programmed cell death, particularly necroptosis at 2 dpe. In rat corneas (N = 4), 5 mg/mL NM caused corneal opacification, punctate keratitis, pupil anisocoria, and decreased corneal sensitivity. At the tissue level at 1-dpe, epithelial cells exhibited a leading edge, the front row of epithelial cells that actively migrate to cover the wound area, with apical layers being c-Casp3 positive and basal and/or wing cells being p-RIPK3 positive. Most corneal cells were γH2AX-positive, and stromal cells were TUNEL-positive but c-Casp3-or p-RIPK3-negative. At 2-dpe, only a few cells were c-Casp3 positive, while most cells on the apical side of the cornea were p-RIPK3 positive. These changes were associated with basement membrane breakdown and tight junction loss in NM-exposed rat corneas. Finally, in cultured porcine corneas, the inhibition of necroptosis resulted in the prevention of corneal tissue destruction caused by NM. Our data suggest that the severity of NM-induced corneal injuries may be linked to increased necroptosis, and targeting necroptosis may reduce or prevent corneal deterioration caused by NM exposure.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110581"},"PeriodicalIF":2.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908025","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":"Corrigendum to “Curcumin ameliorates benzalkonium chloride-induced dry eye disease in mice” [Experiment. Eye Res. 259 (2025) 110509]","authors":"Ziyu Liu ,&nbsp;Yaqiong Li ,&nbsp;Ya Wen,&nbsp;Jiayu Bao,&nbsp;Lei Tian,&nbsp;Ying Jie","doi":"10.1016/j.exer.2025.110555","DOIUrl":"10.1016/j.exer.2025.110555","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"259 ","pages":"Article 110555"},"PeriodicalIF":2.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925530","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":"Response to comment on “Neuroprotective effects of SIRT1 in human RGCs derived from iPSCs following oxidative stress induction at early and late stages of differentiation”","authors":"Suad Abd-Alhadi ,&nbsp;Brahim Chaqour ,&nbsp;Kenneth S. Shindler ,&nbsp;Ahmara G. Ross","doi":"10.1016/j.exer.2025.110594","DOIUrl":"10.1016/j.exer.2025.110594","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110594"},"PeriodicalIF":2.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894776","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":"Suppression of MERTK inhibits proliferation and migration of pterygium fibroblasts","authors":"Junwen Ouyang ,&nbsp;Changyu Wu ,&nbsp;Jingya Yang ,&nbsp;Yun He ,&nbsp;Junpeng Liu ,&nbsp;Boxiao Zhao ,&nbsp;Youmei Zheng ,&nbsp;Boda Li ,&nbsp;Jiaxuan Jiang ,&nbsp;Kai Hu","doi":"10.1016/j.exer.2025.110595","DOIUrl":"10.1016/j.exer.2025.110595","url":null,"abstract":"<div><div>About 10.2 % of people worldwide suffer from pterygium, a proliferative disorder marked by a wing-shaped growth that stretches from corneoscleral limbus to central area. MER proto-oncogene tyrosine kinase (MERTK) has been linked in recent research to the promotion of organ fibrosis and tumor growth. To look into its underlying function and mechanisms, we employed RNA-sequencing methods, MERTK inhibitors, and a series of tests. Primary human pterygium fibroblasts (HPFs) and pterygium tissues both exhibited high expression of MERTK. HPFs' migratory and proliferative capabilities were decreased by MERTK inhibition, which also encouraged an increase in apoptosis. Cell cycle arrest was mechanistically caused by MERTK inhibition. Additionally, further research revealed that this was linked to the downregulation of the ERK/p38 MAPK and PI3K/AKT signaling pathways In addition, MERTK expression was positively correlated with clinical grading, which indicates the degree of pterygium fibrosis. Collectively, targeting MERTK presents a potential therapeutic strategy to limit the proliferation, migration, and fibrosis associated with pterygium. This research may pave a promising way for more effective therapeutic approaches at controlling disease progression.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110595"},"PeriodicalIF":2.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932599","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":"Epithelial and mesenchymal progenitor cells in normal and inflamed human lacrimal glands","authors":"Mohammad Gufran Siddiqui ,&nbsp;Tejaswini Pingali ,&nbsp;Saumya Jakati ,&nbsp;Vivek Singh ,&nbsp;Sayan Basu ,&nbsp;Swati Singh","doi":"10.1016/j.exer.2025.110590","DOIUrl":"10.1016/j.exer.2025.110590","url":null,"abstract":"<div><div>Stem/progenitor cells play an important role in tissue repair and regeneration in response to injury and maintain tissue homeostasis. The existence of the progenitor cells within the human lacrimal gland is established, but their distribution and response to tissue injury are unclear. This study investigated progenitor cells’ distribution and gene expression in normal and inflamed human lacrimal glands. Biopsies from healthy human lacrimal glands (n = 9, 61 ± 14.3 years) and non-specific dacryoadenitis (n = 5; 42.8 ± 19.3 years) were immunostained with progenitor cell markers- Nestin, p63 alpha, CK15, ABCG2, c-kit, and CD90, along with RT-PCR. The basal cell layer of interlobular and intercalated ducts and periacinar spindle-shaped cells expressed progenitor markers. In the dacryoadenitis specimens, lacrimal gland injury was noted as moderate to severe diffuse inflammation and acinar atrophy. The average percentage of positive cells (in ten high-power fields) showed no significant change in dacryoadenitis specimens, except for an increase in CD90. Gene expression revealed a substantial increase in CD90 and reduced expression of ABCG2 and p63α in dacryoadenitis. Double immunostaining with CD73 and CD105 demonstrated predominant CD90 expression in the endothelial cells rather than in the periacinar or periductal regions. The human lacrimal gland has progenitor cells around the intercalated and interlobular ducts that do not increase in severe glandular inflammation. Inflamed lacrimal glands have a demonstrable increase in the expression of MSCs but a reduction in epithelial progenitor cells. Future studies on the interaction between immune and progenitor/stem cells within the lacrimal gland will clarify the mechanisms involved.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110590"},"PeriodicalIF":2.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912355","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":"Teprotumumab reduces the proliferation and viability of pterygium fibroblasts","authors":"Stephen Richard ,&nbsp;Basel Obied ,&nbsp;Jawad Abu-dbai ,&nbsp;Jawad Massalha ,&nbsp;Yakov Rabinovich ,&nbsp;Yoav Vardizer ,&nbsp;Alon Zahavi ,&nbsp;Nitza Goldenberg-Cohen","doi":"10.1016/j.exer.2025.110589","DOIUrl":"10.1016/j.exer.2025.110589","url":null,"abstract":"<div><div>Pterygium is a fibrovascular overgrowth on the ocular surface. There is no effective medical treatment, and the high rate of postoperative recurrence remains a major clinical challenge. We aimed to investigate the ability of teprotumumab (TPT), an insulin-like growth factor 1 receptor antagonist, to reduce human pterygium fibroblast (HPF) viability and proliferation. Primary HPF cultures were derived from excised pterygium tissues from 10 patients scheduled for pterygium surgery, and treated with 10 mg/mL TPT. Cell viability and proliferation were evaluated. DNA damage was measured with TUNEL staining, and ultrastructural changes were visualized by electron microscopy. Quantitative polymerase chain reaction was used to assess the expression of genes involved in growth factor signaling, angiogenesis, and extracellular matrix remodeling. Primary HPF cell lines were successfully established from 5/10 patients. Treatment with TPT significantly reduced HPF viability (29.5 %–50 %) and proliferation (32 %–67 %) across all tested lines. Ki-67-positive cell counts decreased markedly, corroborating the reduced proliferative capacity. TUNEL staining and electron microscopy revealed extensive DNA damage, nuclear fragmentation, and vacuolization. TPT modulated gene expression by downregulating <em>FGF2</em>, <em>VEGFA</em>, and <em>PAI-1</em> expression while upregulating <em>MMP2</em> and <em>MMP3</em> expression, suggesting reduced fibroblast activity and angiogenesis with enhanced extracellular matrix remodeling. TPT demonstrated robust antifibrotic effects on HPFs by reducing their viability and proliferation, inducing DNA damage, and altering the expression of genes associated with fibrosis and angiogenesis. These findings position TPT as a promising therapeutic agent for pterygium, potentially addressing postoperative recurrence and progression. Future animal studies and clinical trials are needed to confirm its efficacy and safety in clinical settings.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110589"},"PeriodicalIF":2.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894774","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":"Lysyl oxidase-like 2 inhibition alleviates subretinal fibrosis in neovascular age-related macular degeneration model","authors":"Xiaowei Yang ,&nbsp;Anping Ma ,&nbsp;Yuan Liu,&nbsp;Zhicheng He,&nbsp;Jianfeng Yu,&nbsp;Shu Su,&nbsp;Jia Chen,&nbsp;Aimin Sang","doi":"10.1016/j.exer.2025.110588","DOIUrl":"10.1016/j.exer.2025.110588","url":null,"abstract":"<div><div>Subretinal fibrosis is a significant contributing factor to the irreversible vision loss linked with neovascular age-related macular degeneration (nAMD). Cellular senescence, a process implicated in the development of nAMD, has been suggested to promote fibrosis through epithelial-mesenchymal transition (EMT). LOXL2 (Lysyl oxidase-like 2) is associated with a variety of fibrotic conditions. However, the role of LOXL2 in subretinal fibrosis remains to be elucidated. In the study, we induced retinal pigment epithelium (RPE) senescence in vitro and in vivo. Further analysis showed that conditioned medium from senescent RPE upregulated the expression of mesenchymal and fibrogenic markers in pre-senescent RPE. LOXL2 silencing was found to attenuate RPE senescence and suppress conditioned medium induced EMT, which was associated with reduced oxidative stress and linked to the TGF-β1/p38 MAPK pathway. In vivo studies confirmed these findings, showing that systemic LOXL2 inhibition reduced D-galactose (D-gal) induced senescence and subretinal fibrosis following laser injury in mice. This treatment also partially corrected the redox imbalance and abnormal activation of TGF-β1/p38 MAPK pathway. The findings indicate that LOXL2 inhibition may be a promising therapeutic approach to prevent subretinal fibrosis in nAMD, providing a novel intervention strategy for a condition for which there are currently no effective treatments.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110588"},"PeriodicalIF":2.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892315","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":"MSC-derived small extracellular vesicles attenuate diabetic retinopathy through miR-29a-3p regulated microglia M1-like polarization","authors":"Jun Tong ,&nbsp;Yueqin Chen ,&nbsp;Ye Zhang ,&nbsp;Cong Liu ,&nbsp;Chang He ,&nbsp;Yajun Liu ,&nbsp;Yinglin Liao ,&nbsp;Fang Chen ,&nbsp;Genhong Yao ,&nbsp;Zhenggao Xie","doi":"10.1016/j.exer.2025.110586","DOIUrl":"10.1016/j.exer.2025.110586","url":null,"abstract":"<div><div>Diabetic retinopathy (DR), considered as a neurovascular disorder, significantly causes permanent vision loss and blindness worldwide among working-age adults. The inflammation caused by M1-like microglia is involved in DR. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) is an attractive candidate for inflammation modulation. However, the regulatory effect of sEVs secreted by MSCs on M1 differentiation of microglia in diabetic retinopathy has not been thoroughly investigated. In this study, intravitreal injection of sEVs reduced retinal inflammation, mitigated vascular leakage, and suppressed M1-like microglia via the HMGB1/TLR4 signaling pathway. Based on MSC-sEVs miRNA sequencing, bioinformatics prediction, and dual-luciferase reporter assay, miR-29a-3p was identified as a key effector in the modulation of M1-like microglia through the down-regulation of HMGB1. The silencing of miR-29a-3p in MSC-sEVs negated their therapeutic efficacy in STZ-induced diabetic rats and human microglial cells (HMC3) treated with advanced glycation end products (AGEs). Silencing miR-29a-3p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on STZ-induced rats and advanced glycation end products (AGEs)-treated HMC3. Additionally, overexpression of miR-29a-3p could suppress M1-like microglia, which could be effectively reversed by overexpressing HMGB1. Overall, this study demonstrated that MSC-sEVs carrying miR-29a-3p attenuate retinal injury in diabetic rats by reducing M1 microglia polarization through the targeting of HMGB1, thereby reducing inflammation and protecting the blood-retinal barrier (BRB). MSC-sEVs and miRNAs may be explored as promising therapeutic targets for DR.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110586"},"PeriodicalIF":2.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892318","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":"Mitochondrial homeostasis dysfunctions during the epithelial-mesenchymal transition process in lens epithelial cells","authors":"Hang Xie ,&nbsp;Rong Huang ,&nbsp;Ke Xu ,&nbsp;Lei Du ,&nbsp;Xingyu Yang ,&nbsp;Weichen Xu ,&nbsp;Xiaoyu Guo ,&nbsp;Guojing Lu ,&nbsp;Tingting Fan ,&nbsp;Changzheng Chen","doi":"10.1016/j.exer.2025.110583","DOIUrl":"10.1016/j.exer.2025.110583","url":null,"abstract":"<div><div>Lens epithelial cells (LECs), the main mitochondria-containing cells in the lens, play a vital role in maintaining lens transparency. Mitochondrial homeostasis is essential for cellular function, yet its changes during epithelial-mesenchymal transition (EMT) in LECs remain unclear. In this study, EMT was induced in LECs using transforming growth factor-β2 (TGF-β2), and mitochondrial function was evaluated through ROS, ATP levels, membrane potential, Mitotracker staining, and electron microscopy. TGF-β2 treatment resulted in mitochondrial dysfunction, evidenced by increased ROS, decreased ATP production, and reduced membrane potential. Mitochondria changed from elongated tubular shapes to fragmented spherical forms. Mitochondrial dynamics were disrupted, with downregulation of fusion proteins (Mfn1, Mfn2, Opa1) and upregulation of fission protein Drp1. Mitophagy was impaired despite activation of the PINK1/Parkin pathway, and mitochondrial biogenesis was suppressed, as shown by decreased expression of PGC-1α and TFAM and reduced mtDNA copy number. These findings highlight a significant imbalance in mitochondrial homeostasis during TGF-β2-induced EMT in LECs, which may contribute to lens opacity and fibrotic cataract formation, offering potential targets for therapeutic intervention.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110583"},"PeriodicalIF":2.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908027","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}