Experimental eye research最新文献

{"title":"FGF21 protects retinal pigment epithelium from sodium iodate-induced injury: Association with inhibition of ferroptosis and the NRF2/GPX4 pathway","authors":"Wanxin Liu ,&nbsp;Lu Wang ,&nbsp;Shuang Jiang","doi":"10.1016/j.exer.2026.110883","DOIUrl":"10.1016/j.exer.2026.110883","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is a leading cause of blindness, with retinal pigment epithelium (RPE) cell death representing a central pathological event. Ferroptosis, an iron-dependent form of regulated cell death, has recently been implicated in RPE degeneration. Although fibroblast growth factor 21 (FGF21) has demonstrated cytoprotective effects in various contexts, its specific role and mechanism in RPE protection, particularly concerning ferroptosis, remain unexplored. This study investigated the protective effect of FGF21 against sodium iodate (NaIO3)-induced damage and its underlying mechanism, with a focus on ferroptosis. In vitro, NaIO3 treatment induced significant injury in ARPE-19 cells, which was effectively rescued by FGF21 co-treatment. The protective efficacy of FGF21 was comparable to that of the specific ferroptosis inhibitor Ferrostatin-1. Mechanistically, FGF21 alleviated intracellular iron overload in ARPE-19 cells by modulating the expression of iron regulators (CD71 and FPN1), reduced lipid peroxidation, and restored glutathione levels. Mechanistic exploration revealed that FGF21 treatment was associated with the upregulation of NRF2 and HO-1 and, crucially, with the attenuation of GPX4 downregulation. In a NaIO3-induced mouse model of retinal degeneration, FGF21 administration significantly preserved retinal structure, as evidenced by the maintained outer nuclear layer and total retinal thickness in optical coherence tomography (OCT) and histological analyses. Consistent with the cellular findings, FGF21 upregulated GPX4, NRF2, and HO-1 protein expression in retinal tissues. Our findings demonstrate that FGF21 protects ARPE-19 cells and the retina from NaIO3-induced damage. Its protective profile is closely associated with the mitigation of key ferroptosis hallmarks and correlates with the modulation of the NRF2/GPX4 antioxidant axis. This study provides novel insights and important preclinical evidence supporting further investigation into FGF21 as a potential therapeutic agent for ferroptosis-related retinal degenerative diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110883"},"PeriodicalIF":2.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036823","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":"Elevated expression of hsa_circ_0053004 in peripheral blood mononuclear cells correlates with endothelial dysfunction in diabetic retinopathy","authors":"Xixi Zhang ,&nbsp;Jiahui Jiang ,&nbsp;Ying Chen ,&nbsp;Juntao Zhang ,&nbsp;Jinglin Zhu ,&nbsp;Zai-Long Chi ,&nbsp;Yufei Wu ,&nbsp;Qinkang Lu","doi":"10.1016/j.exer.2026.110880","DOIUrl":"10.1016/j.exer.2026.110880","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and a leading cause of vision loss. Circular RNAs (circRNAs) have emerged as promising biomarkers, yet their role in DR remains unclear. In this study, peripheral blood mononuclear cells (PBMCs) and aqueous humor samples from patients with diabetes mellitus and DR were analyzed by circRNA microarray, with candidate transcripts validated by real-time quantitative PCR. Receiver operating characteristic analysis was performed to assess diagnostic performance. Functional assays using human retinal microvascular endothelial cells (hRMECs), together with bioinformatic prediction and experimental validation, were employed to explore mechanistic pathways. Among the differentially expressed circRNAs, hsa_circ_0053004 was the most significantly upregulated in DR. Its elevated expression was confirmed in both PBMCs and aqueous humor, and gain-of-function studies demonstrated that hsa_circ_0053004 promotes endothelial dysfunction in hRMECs, at least in part through interactions with miR-139-5p and miR-23a-5p. ROC analysis further revealed its strong discriminative capacity between DR and diabetes mellitus. These findings suggest that hsa_circ_0053004 from PBMCs could serve as a potential diagnostic marker for DR and revealed that it is possibly associated with the pathological mechanisms of DR by affecting endothelial dysfunction.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110880"},"PeriodicalIF":2.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040785","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 letter to the editor, “Significant errors in the paper by Lee R et al.” Ax T. Exp Eye Res. 2025; 263: 110774","authors":"Ryung Lee ,&nbsp;Joshua Ong ,&nbsp;Alex Suh ,&nbsp;Mehmet Kadipasaoglu ,&nbsp;Thomas Mader ,&nbsp;Charles R. Gibson ,&nbsp;John Berdahl ,&nbsp;Andrew G. Lee ,&nbsp;SADES Study Group","doi":"10.1016/j.exer.2026.110857","DOIUrl":"10.1016/j.exer.2026.110857","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110857"},"PeriodicalIF":2.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040756","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":"Extracellular vesicle–mediated delivery of miR-181a-3p confers neuroprotection to degenerating retinal ganglion cells","authors":"Esmahan Durmaz ,&nbsp;Kubra Trabzonlu ,&nbsp;Maryam Esmaeili ,&nbsp;Hanady Nehme ,&nbsp;Lydia Alverez-Erviti ,&nbsp;Yasir Ahmed Syed ,&nbsp;Aled Clayton ,&nbsp;Ben Mead","doi":"10.1016/j.exer.2026.110882","DOIUrl":"10.1016/j.exer.2026.110882","url":null,"abstract":"<div><h3>Background</h3><div>Glaucoma is a progressive optic neuropathy marked by the irreversible degeneration of retinal ganglion cells (RGCs), leading to vision loss. RGC injury is also central to other optic and neurodegenerative conditions, including traumatic optic neuropathy.</div></div><div><h3>Purpose</h3><div>We evaluated whether extracellular vesicles (EVs) derived from retinal precursor cells could serve as an effective platform for the delivery of neuroprotective microRNAs (miRNAs), focusing on miR-181a-3p, to preserve RGC viability and function.</div></div><div><h3>Methods</h3><div>Based on prior profiling of miRNAs differentially expressed in injured RGCs, four candidate miRNAs were screened for neuroprotective effects in primary rat retinal cultures and human embryonic stem cell–derived RGCs. miR-181a-3p, which showed the strongest preservation of RGC survival, was selected for further study. EVs were isolated from R-28 retinal precursor cells, loaded with miR-181a-3p via electroporation, and characterized for particle size, charge, and loading efficiency. EV uptake and neuroprotective efficacy were evaluated <em>in vitro</em> by fluorescence imaging, qPCR, and Ca²⁺-activity assays, and <em>in vivo</em> by intravitreal injection of labelled EVs to assess retinal distribution and cellular uptake.</div></div><div><h3>Results</h3><div>EV-mediated delivery of miR-181a-3p enhanced RGC survival and preserved intracellular Ca²⁺ dynamics compared to free miRNA or lipofectamine-based transfection. EVs improved miRNA stability, enabled selective targeting of retinal cell types, and partially modulated the p38/MAPK signalling axis. EV loading also improved the delivery of miRNA to the retina <em>in vivo.</em></div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that EVs offer a biocompatible, cell-specific, and functionally effective platform for miRNA delivery to the retina. EV-based administration of miR-181a-3p may represent a novel neuroprotective strategy for glaucoma and related optic neuropathies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110882"},"PeriodicalIF":2.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040772","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 transcriptomics combined with spatial proteomics defines phagocytes type-specific immune regulation in diabetic cataract","authors":"Pengfei Li ,&nbsp;Rong wang ,&nbsp;Xiaoxi Qian ,&nbsp;Mengqi Wen ,&nbsp;Zihao Yan ,&nbsp;Xiao Cheng ,&nbsp;Yuxin Dai ,&nbsp;Leyu Zhou ,&nbsp;Xi Zhu ,&nbsp;Wei Chen ,&nbsp;Huaijin Guan ,&nbsp;Min Ji","doi":"10.1016/j.exer.2026.110865","DOIUrl":"10.1016/j.exer.2026.110865","url":null,"abstract":"<div><div>Diabetic cataract (DC) represents a predominant cause of vision impairment among individuals with diabetes, characterized by a multifaceted pathogenesis that encompasses immune-mediated mechanisms. Our objective was to utilize multiomic data to investigate the characteristics of immune cells present in diabetic lenses and to elucidate their underlying mechanisms. Single-cell RNA sequencing (scRNA-seq) was employed to identify cell types and their proportions in lens samples from diabetic and normal rats. Tandem mass tag based quantitative proteomics was then used to screen the in-depth immune targets and mechanism of lens pathological. For the analysis of differential proteins, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed in pathway enrichment assays. Anterior segment optical coherence tomography (AS-OCT) can be used to identify hyperreflective points in diabetic cataract patients. Immunofluorescence staining was performed on anterior capsule membranes from age-related cataract (ARC) and DC patients. scRNA-seq identified five cell types, mononuclear phagocytes as a significant immune cell type in the lens, with increased proportions in diabetic rats compared to normal rats. Further, UCell analysis of macrophage subsets showed that pro-inflammatory M1 macrophages increased significantly and anti-inflammatory M2 macrophages decreased. Subsequently, immunofluorescence staining for the immune cell marker protein CD45 and CD11B on the anterior capsule further confirmed a significantly greater presence of immune cells in DC patients than in ARC patients. AS-OCT findings indicate that the hyper-reflective point on the anterior lens capsule in patients with DC is significantly more pronounced compared to those with ARC. Additionally, AS-OCT is utilized to differentiate between the opacity and clear zone of the LFCs in the enrolled DC patients. Proteomics analysis identified 38 differentially expressed proteins in the opacity zone of LFCs compared to the clear zone in DC patients, comprising 17 upregulated and 21 downregulated. Among them, the significantly upregulated protein MIF is an important macrophage chemokine, which may play a crucial regulatory role in mediating lens immunity. GO and KEGG pathway analyses revealed associations with immune regulation and protein ubiquitination pathways, particularly in the activation of lymphocytes and leukocytes, and K63 ubiquitination. Our study provides evidence for the involvement of immune mechanisms, particularly mononuclear phagocytes, in the development of DC. The upregulation of immune regulation and alterations in protein ubiquitination pathways suggest potential therapeutic targets for DC. Further investigation is essential to understand the specific functions of these immune cells and to design targeted therapies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110865"},"PeriodicalIF":2.7,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017971","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":"Duplex droplet digital PCR (ddPCR) improves the diagnosis of Aspergillus and Fusarium keratitis","authors":"Yamini Tawde ,&nbsp;Sourav Das ,&nbsp;Shreya Singh ,&nbsp;Soham Basak ,&nbsp;Savitri Sharma ,&nbsp;Amit Gupta ,&nbsp;Amanjit Bal ,&nbsp;Shivaprakash M. Rudramurthy ,&nbsp;Geetika Yadav ,&nbsp;Anup Ghosh","doi":"10.1016/j.exer.2026.110866","DOIUrl":"10.1016/j.exer.2026.110866","url":null,"abstract":"<div><div>Fungal keratitis (FK) is a serious corneal infection leading to blindness. The present study aims to develop a duplex ddPCR for the detection of <em>Aspergillus</em> sp. and <em>Fusarium</em> sp. causing FK and also to enhance the diagnostic accuracy by evaluating the sensitivity of ddPCR in comparison to qPCR. This Prospective, multicentric study was conducted from November 2019 to August 2021, including three healthcare facilities across India. All patients suspected with FK were included in the study. A part of the collected corneal samples was used for routine microbiological workup and another part of the sample was used for the standardization and validation of ddPCR. A total of 42 corneal buttons were used for standardisation. <em>Aspergillus</em> primer concentration of 750nM showed highest sensitivity of 81.48 % with 93.33 % specificity at ct-value 14.05 while 900 nM primer concentration was best for <em>Fusarium</em> with 80 % sensitivity and 96.3 % specificity at ct-value 83.65. Probe concentrations for both <em>Aspergillus</em> and <em>Fusarium</em> were 250 mM. Validation cohort included 74 corneal samples, <em>Aspergillus</em> ddPCR demonstrated 84.21 % sensitivity with 94.64 % specificity while <em>Fusarium</em> ddPCR had 75 % sensitivity with a specificity of 96.3 %. The comparative analysis demonstrated an improvement in diagnostic performance by ddPCR for both <em>Aspergillus</em> and <em>Fusarium</em> compared to recently reported genus-specific real-time PCR. The ddPCR noticeably enhanced the diagnostic performance for both <em>Aspergillus</em> and <em>Fusarium</em> FK in comparison to the genus-specific real-time PCR. Thus, ddPCR can serve as a rapid technique holding a challenge over conventional and qPCR for FK diagnosis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110866"},"PeriodicalIF":2.7,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003290","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":"Integrated proteomic profiling of aqueous humor reveals CDC42/RHOA-mediated pathogenic mechanisms in nAMD and PDR","authors":"Lingjie Kong ,&nbsp;Siyi Qi ,&nbsp;Xiaoyan Han ,&nbsp;Jingyue Zhang ,&nbsp;Linyu Zhang ,&nbsp;Duo Li ,&nbsp;Qin Jiang ,&nbsp;Shujie Zhang ,&nbsp;Chen Zhao","doi":"10.1016/j.exer.2026.110871","DOIUrl":"10.1016/j.exer.2026.110871","url":null,"abstract":"<div><div>Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR), though clinically distinct, are both sight-threatening ocular disorders driven by pathological neovascularization. However, their shared molecular mechanisms remain poorly characterized. In this study, we performed DIA quantitative proteomic analysis of aqueous humor (AH) from patients with nAMD, PDR, and control. A total of 3186 proteins were identified, in which 877 and 1017 differentially expressed proteins (DEPs) were detected in the nAMD and PDR groups, respectively, compared to control group. Functional enrichment analysis revealed significant involvement of inflammatory and metabolic pathways in both diseases. Notably, the persistent upregulation of cell division cycle 42 (CDC42) and ras homolog family member A (RHOA) in nAMD and PDR, combined with their established role in cytoskeletal remodeling, suggests their significant involvement in pathological angiogenesis. These findings offer novel perspectives on shared pathogenic pathways in neovascular ocular disorders and suggest potential therapeutic targets for further investigation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110871"},"PeriodicalIF":2.7,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003258","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":"Resveratrol alleviated diabetic retinal neuronal ferroptosis induced by high glucose through inhibiting HIF-1α and HMOX1 pathway","authors":"Meng Ye ,&nbsp;Yan Jiang ,&nbsp;Hongya Gong ,&nbsp;Chaowu Wu ,&nbsp;Tao Li ,&nbsp;Xuhui Chen","doi":"10.1016/j.exer.2026.110872","DOIUrl":"10.1016/j.exer.2026.110872","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a common complication of diabetes mellitus that can cause blindness and affect the life quality of patients. Diabetic retinal neurodegeneration (DRN) caused by high glucose might be the earlier pathological change preceding vascular injury. Resveratrol has been showed to have therapeutic effects on DRN but the mechanism remains unclear. Ferroptosis is a new form of regulated cell death and has been found to be involved in DRN. In this study, we found genetic relationship between resveratrol and ferroptosis in DRN pathogenesis using bioinformatics analysis and demonstrated HIF-1α and HMOX1 as the hub genes. Our study established <em>in vitro</em> model of DRN in high-glucose cultured SH-SY5Y cells and found ferroptosis processes characterized of reactive oxygen species (ROS) accumulation and cellular mitochondrial damage along with upregulation of HIF-1α and HMOX1. Application of resveratrol alleviated high glucose-induced ferroptosis phenotypes in SH-SY5Y cells through inhibiting HIF-1α and HMOX1. We also confirmed ferroptosis process and RGC damage in diabetic (db/db) mouse model. The upregulation of HIF-1α and HMOX1 was also found in diabetic mouse retina. By resveratrol gavage, RGC damage in diabetic (db/db) mouse model was alleviated and the expression level of HIF-1α and HMOX1 in retina was decreased. Our study revealed the involvement of ferroptosis process in retinal neurodegeneration and might provide new insights into neuroprotective interventions in diabetic retinopathy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110872"},"PeriodicalIF":2.7,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003456","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 morphology in spinocerebellar ataxia type 1 (SCA1) mice: A stereological analysis across different age groups","authors":"Olena Yakushko ,&nbsp;Jan Cendelin ,&nbsp;Zbynek Tonar ,&nbsp;Yaroslav Kolinko","doi":"10.1016/j.exer.2026.110869","DOIUrl":"10.1016/j.exer.2026.110869","url":null,"abstract":"<div><div>Spinocerebellar ataxia type 1 (SCA1) affects not only the cerebellum but also the retina; however, retinal pathology remains poorly characterised in murine models of SCA1. To fill this gap, we performed a comprehensive stereological analysis of the retinal structure of SCA1^{<em>154Q/2Q</em>} knock-in mice and their healthy SCA1^2Q/2Q littermates at 6 and 10 months of age. We compared animals across genotypes at each age and across ages within each genotype. Using unbiased stereology, we quantified the total retinal volume, volumes of individual retinal layers, total photoreceptor numbers, numbers of rods and cones, and total cell numbers in the inner nuclear and ganglion cell layers. Structural abnormalities, including disorganisation of photoreceptor outer segments and reduced volumes of both photoreceptor inner and outer segments, were evident in SCA1 mice as early as 6 months. By 10 months, these alterations had progressed, with a decrease in the number of ganglion cells and a reduced proportion of cones among the total photoreceptors. Wild-type mice also exhibited age-related changes, but the pattern and magnitude differed, suggesting distinct mechanisms of normal ageing versus SCA1-related neurodegeneration. Our findings demonstrate that retinal remodelling in SCA1 mice parallels changes observed in human patients, validating this model for investigating visual system involvement in SCA1. These results emphasize the need to consider retinal pathology when interpreting behavioural or motor deficits and in designing future preclinical interventions.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110869"},"PeriodicalIF":2.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996369","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":"TLR9-mediated activation of the NLRP3 inflammasome in Fusarium solani-induced keratitis","authors":"Yanqing Zhang ,&nbsp;Yi Lin ,&nbsp;Yani Zhang ,&nbsp;Hanfeng Tang,&nbsp;Jianzhang Hu,&nbsp;Bing Wang","doi":"10.1016/j.exer.2026.110867","DOIUrl":"10.1016/j.exer.2026.110867","url":null,"abstract":"<div><div>Toll-like receptor 9 (TLR9) is a crucial innate immune receptor that recognises pathogenic DNA and initiates downstream inflammatory signaling, yet its function in fungal keratitis remains poorly defined. This study aimed to clarify the specific role of TLR9 in <em>Fusarium solani</em> (<em>F. solani</em>) –induced keratitis and to provide mechanistic insights for targeted therapy. A murine model of <em>F. solani</em> keratitis was established to examine the expression and regulation of TLR9 and NLRP3. RNA sequencing, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence were used to assess gene and protein expression. The activities of TLR9 and NLRP3 were modulated by adeno-associated virus short hairpin RNA (AAV-shRNA), small interfering RNA (siRNA), and pharmacological agents (Nig and MCC950). Disease severity and histopathological alterations were evaluated by slit-lamp examination, clinical scoring, and hematoxylin–eosin staining, while protein interactions were analysed through molecular docking and immunocolocalization. TLR9 and NLRP3 were markedly up-regulated in <em>F. solani</em>–infected corneas. TLR9 silencing suppressed nuclear factor κB (NF-κB) and NLRP3 activation, thereby mitigating corneal inflammation, reducing stromal oedema, limiting inflammatory cell infiltration, and lowering IL-1β production. Pharmacological inhibition of NLRP3 with MCC950 produced similar protective effects, whereas activation by nigericin reversed these benefits. In conclusion, TLR9 functions as a pivotal upstream regulator of the NLRP3 inflammasome in <em>F. solani</em> keratitis. These findings uncover a mechanistic link between TLR9 signaling and inflammasome-mediated inflammation, highlighting TLR9 as a potential immunomodulatory target for fungal keratitis therapy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110867"},"PeriodicalIF":2.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997688","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}