Experimental eye research最新文献

{"title":"Commonalities between fibrotic and inflammatory mechanisms in proliferative vitreoretinopathy and proliferative diabetic retinopathy","authors":"Anirudh Sreenivas BK ,&nbsp;Sriram Simakurthy ,&nbsp;P. Mahesh Shanmugam ,&nbsp;Sangeeta Nath ,&nbsp;Trichur R Raju","doi":"10.1016/j.exer.2025.110482","DOIUrl":"10.1016/j.exer.2025.110482","url":null,"abstract":"<div><div>Proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) are vision-threatening retinal diseases characterized by pathological fibrosis and epiretinal membrane (ERM) formation. While PDR is primarily driven by chronic hyperglycemia associated with diabetes, PVR typically arises secondary to retinal detachment or ocular trauma, both conditions share common mechanisms with respect to fibrosis and inflammation. These mechanisms are orchestrated by a complex interplay of inflammatory cytokines, growth factors, and extracellular matrix (ECM) remodeling.</div><div>Fibrosis and inflammation play central roles in both diseases. Transforming growth factor-beta (TGF-β) is a key profibrotic cytokine that induces epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and endothelial-to-mesenchymal transition (EndoMT) in vascular endothelial cells, driving fibrotic membrane formation. Additional growth factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and connective tissue growth factor (CTGF) further contribute to fibroproliferative membrane formation in PVR and fibrovascular membrane formation in PDR. This process is also exacerbated by pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and various interleukins, which amplify cellular activation and ECM deposition. Emerging evidence also highlights the modulatory roles of exosomes, long non-coding RNA, microRNAs, and metabolic alterations in shaping the fibrotic microenvironment.</div><div>This review also outlines current treatment modalities in both diseases, including surgical and adjuvant-based approaches. However, these therapeutic approaches are only validated in pre-clinical animal models, which often do not replicate human conditions. Lower efficiency and the need for repetitive applications make prognosis very difficult. Moreover, patient-to-patient variability in disease manifestation and lack of a definite biomarker also add to the complexity. Emerging therapeutics shift focus towards personalized medicine with modulations at the gene and cell levels to achieve better clinical efficiency. A deeper understanding of the shared microenvironmental drivers of fibrosis and inflammation in PDR and PVR may pave way for more effective and targeted therapies to prevent vision loss in these devastating retinal disorders.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110482"},"PeriodicalIF":3.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274545","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":"Expression and the pro-fibrotic effects of Mesenchyme homeobox 1 in patients with pterygium","authors":"Wanna Li ,&nbsp;Xiaofei Zhao ,&nbsp;Yihan Zhao ,&nbsp;Chenzhao Ma ,&nbsp;Jiawei Wang ,&nbsp;Jianqiao Li","doi":"10.1016/j.exer.2025.110479","DOIUrl":"10.1016/j.exer.2025.110479","url":null,"abstract":"<div><div>Pterygium is an usual ocular disease characterised by uncontrolled overgrowth conjunctive tissue invasion of the cornea. The aim of this research was to determine the expression of Mesenchyme Homeobox 1(MEOX1) in excised pterygium tissues, and to identify whether MEOX1 participates in the pathogenesis of pterygium. Subjects with primary pterygium and strabismus correction surgeries were included for this study. The expression levels of MEOX1 in all of the slides were evaluated using immunohistochemistry or quantitative Real-Time PCR (qRT-PCR). The relation between clinicopathological traits and MEOX1 expression was identified through Pearson correlation coefficient. Primary human pterygium fibroblasts (HPFs) and conjunctival fibroblasts (HConFs) were isolated and cultured in vitro. Cell proliferation and migration were assessed using Ki-67 staining and wound healing assays, respectively. Downstream of MEOX1 pathway was determined by Western blot. Immunohistochemistry showed nuclear-enriched MEOX1 localization with marked overexpression in pterygium tissues compared to controls. Moreover, MEOX1 overexpression demonstrated significant positive correlation with pterygium limbal invasion length. In vitro tests, knockdown of MEOX1 significantly inhibited HPFs’ proliferation, migration and differentiation to myofibroblast. Besides, Western blot analysis revealed a significant upregulation of alpha-smooth muscle actin (α-SMA) in HPFs, while MEOX1 inhibition substantially suppressed the expression. Our results firstly found markedly elevated MEOX1 expression levels in pterygium tissues, with expression intensity showing a significant positive correlation with the invasive length of pterygium (r = 0.657, <em>p</em> = 0.006). In vitro, MEOX1 played a significant role in regulating the proliferation and migration of HPFs through the α-SMA pathway. These findings illuminate the potential role of MEOX1 in the pathogenesis of pterygium.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110479"},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247188","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":"AAV2.7m8 transduction of stage 2 human retinal organoids induces highly variable responses in innate and inflammatory gene expression and cytokine secretion","authors":"Monica M. Sauter ,&nbsp;Hongyu Rao Noel ,&nbsp;Divya Sinha ,&nbsp;Emma C. Nelson ,&nbsp;Mai N. Xiong ,&nbsp;David M. Gamm ,&nbsp;Curtis R. Brandt","doi":"10.1016/j.exer.2025.110478","DOIUrl":"10.1016/j.exer.2025.110478","url":null,"abstract":"<div><div>The preclinical evaluation of recombinant AAV (rAAV) gene therapy vectors should consider host innate and inflammatory immune responses which can cause harmful ocular inflammation and decrease the efficiency of transgene delivery. In this study we determined which cell types expressed the transgene following transduction of 75-day-old human pluripotent stem cell (hPSC)-derived retinal organoids (RO) with the gene delivery vector AAV2.7m8-CAG-EGFP (AAVGFP). We then examined the changes in RO inflammatory gene expression and cytokine secretion following AAVGFP transduction. Our results indicated that RO cell types including photoreceptors (PR), retinal progenitor cells (RPCs), retinal ganglion cells (RGC), horizontal cells, and amacrine cells were transduced by AAVGFP. PCR array analysis following AAVGFP RO transduction detected up regulation of innate and adaptive immune response genes including chemokine (CC) genes, cluster of differentiation (CD) genes, interleukin (IL) genes, and transcription factors. The changes in gene expression following RO transduction varied drastically depending on the manufacturer and the production lot of AAVGFP, and were also not consistent between RO batches transduced with the same lot of AAVGFP. Analysis of RO supernatants indicated that several pro- and anti-inflammatory cytokines including sCD40L, IL-4, IL-6, IL-10, IL-13, IL-17A and MCP-1 were secreted following AAVGFP transduction, but the secretion pattern of these cytokines varied between transductions. These data indicate that intermediate-stage differentiating human ROs derived from the same hPSC line have highly variable responses to rAAV gene delivery vectors.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110478"},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247187","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":"“Healing effect of homeopathic drug Theranekron in an alkaline-induced corneal injury model in rats”","authors":"N.F. Karakuyu ,&nbsp;M.N. Kaya ,&nbsp;G. Usta Sofu ,&nbsp;E. Sarman","doi":"10.1016/j.exer.2025.110464","DOIUrl":"10.1016/j.exer.2025.110464","url":null,"abstract":"<div><div>Corneal injuries, particularly those caused by alkaline substances, are challenging to treat and can lead to severe complications such as inflammation, ulceration, and blindness. Current treatments, including lavage, antibiotics, and steroids, often fail to provide rapid or complete recovery. Theranekron, a homeopathic preparation derived from the venom of the Tarantula cubensis spider, has shown anti-inflammatory and wound-healing properties in veterinary medicine. This study aimed to investigate Theranekron's potential in treating corneal damage in a rat model. Thirty-two rats were divided into four groups: damage, damage + dexamethasone, damage + ocular Theranekron, and damage + subcutaneous Theranekron. Corneal damage was induced using silver/potassium nitrate sticks, and treatments were administered for seven days. Clinical, histopathological, and immunohistochemical evaluations were conducted to assess inflammation, neovascularization, and tissue repair. Rats treated with Theranekron (both ocular and subcutaneous) showed significant reductions in inflammation, edema, and neovascularization compared to the untreated and dexamethasone groups. Immunohistochemical analysis revealed lower expression of inflammatory markers (TNF-α, NF-κB-p65) and VEGF in Theranekron-treated groups. Theranekron exhibited significant potential in promoting corneal healing by reducing inflammation and inhibiting neovascularization. Its effectiveness exceeds dexamethasone's, making it a promising alternative for treating corneal injuries. Further research is needed to explore its application in human ocular medicine and to optimize dosing and administration methods.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110464"},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144243557","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":"Nrf2-HO1 signaling pathway-mediated axial elongation in lens-induced myopia in Guinea pigs through regulation of tight junctions in retinal pigment epithelial cells","authors":"He-Yan Li ,&nbsp;Li Dong ,&nbsp;Rui-Heng Zhang ,&nbsp;Wen-Da Zhou ,&nbsp;Hao-Tian Wu ,&nbsp;Xu-Han Shi ,&nbsp;Chu-Yao Yu ,&nbsp;Yi-Tong Li ,&nbsp;Jost B. Jonas ,&nbsp;Wen-Bin Wei","doi":"10.1016/j.exer.2025.110477","DOIUrl":"10.1016/j.exer.2025.110477","url":null,"abstract":"<div><div>The study aimed to explore the potential involvement of Nrf2-HO1 (nuclear factor erythroid 2-related factor 2 heme oxygenase-1) in the process of myopic axial elongation, which influenced the disruption of tight junctions in retinal pigment epithelium (RPE) cells. Guinea pigs aged 2–3 weeks underwent bilateral lens-induced myopization (LIM) and received weekly intraperitoneal injections of the heme oxygenase-1 (HO-1) activators Hemin (25 mg/kg and 50 mg/kg, respectively), or Quercetin (25 mg/kg and 50 mg/kg, respectively). The study additionally included normal control groups with or without LIM and with vehicle injections. Ocular biometry, optical coherence tomography, and high-throughput sequencing were performed. Eyes with LIM showed a significantly increased expression of the Nrf2-HO1 signal pathway. Eyes with Hemin injections demonstrated axial elongation in a Hemin-dose dependent manner. Eyes with LIM and Quercetin injections showed in a dose-dependent manner and inhibition of the Nrf2 overexpression and an attenuation of axial elongation, a disruption of RPE cell tight junctions, and retinal and choroidal thinning. Immunofluorescence revealed the RPE cell as the main location of the HO-1 activation. Transmission electron microscope showed that Hemin was associated with a disruption of RPE tight junctions with axial elongation. The overexpression of Nrf2-HO1 signal pathway may be involved in LIM development and RPE tight junction disruption. The potential anti-myopic therapeutic value of Quercetin may be further explored.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110477"},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144243558","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":"miR-29a regulates scleral remodelling via TLR7/8-dependent inflammatory signalling in myopia","authors":"Lingfeng Lv ,&nbsp;Qing Shao ,&nbsp;Jibo Zhou ,&nbsp;Yi Zhu","doi":"10.1016/j.exer.2025.110474","DOIUrl":"10.1016/j.exer.2025.110474","url":null,"abstract":"<div><div>Myopia, especially high myopia, is a global health concern with a rising prevalence, yet its underlying mechanisms remain incompletely understood. MicroRNAs (miRNAs) have been implicated in the pathogenesis of myopia, potentially playing a critical role in its development. This study aimed to investigate the mechanism by which miR-29a mediates scleral remodelling through the activation of Toll-like receptors (TLRs). By using a form-deprivation myopia (FDM) guinea pig model, we combined fluorescence in situ hybridization (FISH) and qPCR to demonstrate that the expression of miR-29a and inflammatory cytokines (TNF-α and IL-6) was significantly upregulated in the sclera of myopic eyes, whereas TLR7/8 expression remained unchanged. In human scleral fibroblasts (HSFs), FISH and RNA immunoprecipitation (RIP) assays revealed that miR-29a directly interacts with TLR7 and TLR8, forming ligand‒receptor complexes. This interaction activated downstream inflammatory signalling, leading to upregulated expression of proinflammatory cytokines (TNF-α and IL-6), downregulated expression of anti-inflammatory IL-10, and suppression of COL1A1 expression. Inhibition of TLR7/8 signalling reversed these effects, restoring COL1A1 levels and attenuating inflammatory responses. Our findings reveal a novel mechanism by which miR-29a promotes scleral remodelling through TLR7/8-mediated inflammatory signalling, providing new insights into the pathogenesis of myopia and potential therapeutic targets for its prevention and treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110474"},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144243559","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":"The impact of break schedules on digital eye strain symptoms and ocular accommodation during prolonged near work","authors":"Beatriz Redondo ,&nbsp;Raimundo Jiménez ,&nbsp;Jesús Vera ,&nbsp;Mark Rosenfield","doi":"10.1016/j.exer.2025.110463","DOIUrl":"10.1016/j.exer.2025.110463","url":null,"abstract":"<div><div>This study evaluated the effects of four different break schedules on symptoms and signs of Digital Eye Strain (DES) during a 40-min reading task. Twenty-four young adults participated in four experimental conditions, performed on four different days in random order: no break, one break at 20 min, one break every 10 min and self-paced breaks. Primary outcomes included visual symptoms reported after the reading task, accommodative lag and variability during the reading task, and the near work-induced transient myopia (NITM) assessed post-task (including initial NITM and its decay). Visual symptoms were evaluated using a 10-item questionnaire, while accommodative measures were obtained with a binocular open-field autorefractor (Grand Seiko WAM-5500). Participants reported higher “eye irritation or burning” in the no-break condition compared to the 3-break (p &lt; 0.001) and self-paced breaks conditions (p = 0.008). Eye strain was also greater in the no-break condition than in the 3-break (p = 0.04) and self-paced breaks conditions (p = 0.04). Accommodative variability showed significant effects for both break schedule (p = 0.03) and time period (p = 0.02), with greater variability observed in the no-break and 3-break conditions during the final time interval. NITM was higher in the no-break condition compared with the 3-break (p = 0.02) and self-paced breaks conditions (p = 0.02), while NITM decay was faster in the 3-break condition (p = 0.001). Accommodative lag did not differ significantly across conditions. These findings highlight the potential benefits of individualized and frequent breaks for managing DES during prolonged screen use.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110463"},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223321","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 the 12-hour ultradian rhythm in ocular surface microbiota of T2DM C57BL/6J mice","authors":"Xinwei Jiao ,&nbsp;Hongyu Li ,&nbsp;Ting Wang ,&nbsp;Hongchen Fu ,&nbsp;Shiwu Wang ,&nbsp;Hong Liu ,&nbsp;Lei Wang ,&nbsp;Xiuyun Li ,&nbsp;Aijun Deng ,&nbsp;Zhijie Li","doi":"10.1016/j.exer.2025.110472","DOIUrl":"10.1016/j.exer.2025.110472","url":null,"abstract":"<div><div>The ocular surface (OS) microbiota exhibits a 12-h ultradian rhythm in healthy mice, essential for ocular homeostasis, yet its regulation in type 2 diabetes mellitus (T2DM), associated with ocular surface diseases, remains unclear. This study investigated the temporal dynamics of the OS microbiota in control (NC) and T2DM C57BL/6J mice over a 24-h cycle (ZT0, ZT6, ZT12, ZT18) using 16S rRNA sequencing and JTK_CYCLE analysis of diversity indices, OTU composition, and family-level abundance. In NC mice, a robust 12-h rhythm with distinct temporal patterns was observed. In contrast, T2DM disrupted this rhythmicity, with diversity indices and OTU compositions lacking temporal structure, and family-level rhythms, including those of <em>Rhodocyclaceae</em> and <em>Pseudomonadaceae</em>, altered, often shifting toward 24-h patterns in selected taxa and diversity measures. PCoA confirmed significant temporal clustering in NC but not in T2DM. These findings suggest that T2DM disrupts the 12-h ultradian rhythm of the OS microbiota, inducing complex temporal dysregulation, potentially contributing to ocular pathology, and highlight the potential of chronotherapeutic strategies to restore microbial rhythmicity and alleviate T2DM-related complications.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110472"},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223323","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":"DAPL1 inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells by regulating the TGF-β/MITF pathway","authors":"Yaqi You ,&nbsp;Youjia Liu ,&nbsp;Lijing Huang ,&nbsp;Wan-ni Lu ,&nbsp;Yingxin Zhang ,&nbsp;Tianyin Nie ,&nbsp;Meiyu Jing ,&nbsp;J. Fielding Hejtmancik ,&nbsp;Xingyi Li ,&nbsp;Ling Hou ,&nbsp;Xiaoyin Ma","doi":"10.1016/j.exer.2025.110473","DOIUrl":"10.1016/j.exer.2025.110473","url":null,"abstract":"<div><div>Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a critical factor in the development of retinopathies, including proliferative vitreoretinopathy (PVR) and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. Deficiency in DAPL1 can induce RPE-EMT in vivo, and <em>Dapl1</em> knockout mice (<em>Dapl1 −/−</em>) are prone to PVR, while aged <em>Dapl1 −/−</em> mice display AMD-like pathological features. However, the molecular mechanisms through which DAPL1 regulates RPE-EMT remain largely unknown. Here, using <em>Dapl1 −/−</em> mice and DAPL1 knockdown or overexpression RPE cells, we show that DAPL1 inhibits RPE-EMT by regulating the TGF-β/MITF signaling pathway, a critical signaling pathway/transcription factor in RPE cells. Overexpression of DAPL1 inhibits TGF-β-induced RPE-EMT, while deletion of <em>Dapl1</em> in mice activates TGF-β signaling, decreases MITF expression, and promotes RPE-EMT under physiological or PVR pathological conditions. Gene therapy demonstrates that transgenic overexpression of MITF in <em>Dapl1 −/−</em> mice inhibits RPE-EMT in vivo and prevents retinal detachment-induced PVR pathological progress, offering hope for future treatment. Similarly, pharmacological therapy with Isoviolanthin, a flavonoid glycoside isolated from traditional medicinal herbs, inhibits TGF-β signaling and increases MITF expression in RPE cells in <em>Dapl1 −/−</em> mice, which then effectively rescues experimental PVR in <em>Dapl1 −/−</em> mice. These results suggest that DAPL1 regulates RPE-EMT at least partial through the TGF-β/MITF pathway and that targeting the TGF-β/MITF pathway could be a potential therapeutic strategy to treat <em>Dapl1</em> deficiency-induced RPE-EMT-related retinal diseases, instilling hope for the future of retinal disease treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110473"},"PeriodicalIF":3.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212948","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":"Integrin αvβ6 mediates the effects of age-related decreases in matrix stiffness on Tenon's fibroblast activation and bleb scarring in glaucoma","authors":"Lemeng Feng ,&nbsp;Wei Xiong ,&nbsp;Jiayang Yin ,&nbsp;Dongshi Guan ,&nbsp;Hangyu Li ,&nbsp;Jiamin Cao ,&nbsp;Ziyi Zhu ,&nbsp;Wenhua Zhang ,&nbsp;Feng Zhang","doi":"10.1016/j.exer.2025.110459","DOIUrl":"10.1016/j.exer.2025.110459","url":null,"abstract":"<div><div>Glaucoma, including primary open-angle glaucoma (POAG) and primary angle-closure glaucoma, leads to optic nerve injury and visual field loss, often necessitating surgical intervention to lower intraocular pressure (IOP). Trabeculectomy, the most common glaucoma surgery, could fail due to excessive scarring of the filtering bleb, driven by the hyperproliferation of human Tenon's fibroblasts (HTFs). Herein, the impact of aging on matrix stiffness in Tenon's capsule tissue, the role of extracellular matrix (ECM) stiffness in the phenotypic transformation of HTFs, and the regulatory function of integrin alphavbeta6 (αvβ6) were investigated. Matrix stiffness in Tenon's capsule tissue is notably lower in elder glaucoma patients in comparison with younger ones, with reduced levels of α-SMA, collagen I, and integrin αvβ6. GFS (Glaucoma Filtration Surgery) models were established in young and old SD rats, and it was observed that older rats exhibited lower ECM stiffness, reduced fibrosis, and decreased integrin αvβ6 expression. HTFs from elderly glaucoma patients showed reduced ECM stiffness, decreased viability, impaired migration, and diminished fibrotic responses. When HTFs from young glaucoma patients were cultured on substrates of varying stiffness, it was found that stiffer substrates increased cell viability, migration, collagen synthesis, and fibrosis marker expression. Additionally, knocking down integrin αvβ6 in HTFs cultured on stiffer substrates resulted in decreased cell viability, impaired migration, reduced collagen synthesis, and lower fibrosis marker expression. <em>In vivo</em> knockdown of integrin αvβ6 effectively reduced ECM stiffness and fibrosis, thereby attenuating bleb scarring after GFS in young rats. Collectively, the aging-associated changes in ECM stiffness and integrin αvβ6 expression contribute to reduced fibrosis, potentially enhancing the success of trabeculectomy in elder patients.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110459"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215378","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}