Experimental eye research最新文献

{"title":"Automated segmentation of pterygium lesions using multiscale deep learning networks","authors":"Mohd Asyraf Zulkifley","doi":"10.1016/j.exer.2026.110928","DOIUrl":"10.1016/j.exer.2026.110928","url":null,"abstract":"<div><div>Pterygium is an eye condition that needs to be identified at an early stage so that its progression can be mitigated in order to avoid the possible threat of visual impairment. One of the important low-level modules in determining the severity level of the pterygium automatically is to measure the extent of fibrovascular tissue encroachment onto the corneal and pupil regions. Therefore, it is important to develop a semantic segmentation method to map and quantify the lesion tissues accurately, especially through the deep learning technique. As the pterygium condition progresses from the trace stage to the severe stage, the lesions will generally become bigger but maintain more or less the same shape, which looks like a wedge. Taking inspiration from this unique pattern of pterygium lesions, this work aims to explore multiscale deep learning networks to capture the variable scales of the lesion features effectively. All the proposed multiscale modules are embedded at the bottleneck layer of the base UNet architecture, whereby the feature map size is the smallest to reduce the potential increment in the computational burden. Apart from that, the total number of convolutional channels is fixed to 1024, whereby the multiscale module replaces the first convolutional set at the UNet's bottleneck layer. Two main multiscale modules have been explored, which are spatial pyramid pooling (SPP) and atrous spatial pyramid pooling (ASPP) modules. Furthermore, each of these modules has been expanded by analyzing the equal-flow (EF) and waterfall-flow (WF) patterns in constructing the parallel paths that represent the multiscale features. According to the simulation results, the best segmentation network is UNet, which has been embedded with three parallel paths of the EF-ASPP module that produces the lowest Hausdorff distance of 16.75 pixels. As a result, the severity level of pterygium can be better predicted through accurate extraction of the lesion map. This work can be further improved by analyzing different network architectures of the multiscale module, especially networks that focuses on the larger feature maps size, but surely with a trade-off in computational burden.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110928"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192727","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":"Viral microRNA inhibition enhances antiviral immunity by modulating corneal inflammatory and resolution pathways in HSV-1 induced keratitis","authors":"Chandrashekhar D. Patil ,&nbsp;Raza Ali Naqvi ,&nbsp;Araceli Valverde ,&nbsp;Hemant Borase ,&nbsp;Afsar R. Naqvi ,&nbsp;Deepak Shukla","doi":"10.1016/j.exer.2026.110903","DOIUrl":"10.1016/j.exer.2026.110903","url":null,"abstract":"<div><div>Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious corneal blindness worldwide. Viral persistence and disease severity are strongly influenced by the virus's ability to modulate host immune responses; however, the mechanisms by which HSV-1 alters corneal immunity are incompletely understood. In particular, the role of virus-encoded microRNAs (v-miRs) in shaping corneal immune responses during herpes simplex infection remains unclear. We previosuly showed that inhibition of selected HSV-1 v-miRs reduced viral replication and disease severity in a mouse model of ocular infection. Building on these findings, the present study investigated how v-miR inhibition affects corneal immune responses. Using corneal tissue RNA from HSV-1-infected mice, we performed an immune profiling PCR array by analyzing the expression of 88 genes associated with immune cell markers and polarization states. Topical inhibition of miR-H1-5p, miR-H3-3p, and miR-H6-3p resulted in distinct patterns of immune gene expression compared with the control treatment. Inhibition of these v-miRs altered 16, 31, and 57 immune-related genes, respectively, spanning both myeloid- and lymphoid-associated pathways. Notably, the anti-inflammatory genes <em>Arg</em><em>1</em> and <em>Il10</em> were consistently upregulated across all v-miR inhibitor-treated groups. In parallel, increased expression of the pro-resolution enzymes <em>15-lox</em> and <em>Alox5</em> suggested enhanced engagement of resolution pathways. Mechanistic studies demonstrated that v-miRs directly target immune regulatory genes through binding sites within their untranslated regions. Together, these findings suggest that HSV-1 v-miRs contribute to corneal immunopathology by suppressing anti-inflammatory and pro-resolving immune pathways, and that targeted inhibition of v-miRs may promote immune resolution during HSV-1–induced keratitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110903"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131660","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 and nitrosylomic profiling suggests a role for S-nitrosylation in choroidal dysregulation during myopia pathogenesis","authors":"Yuhang Liu ,&nbsp;Xiaohang Chen ,&nbsp;Ji Kou ,&nbsp;Xiangyi Wen ,&nbsp;Longqian Liu","doi":"10.1016/j.exer.2026.110909","DOIUrl":"10.1016/j.exer.2026.110909","url":null,"abstract":"<div><h3>Background</h3><div>Myopia, a global health burden, is associated with choroidal dysfunction, but the role of post-translational modifications, specifically S-nitrosylation (SNO), in its pathogenesis remains unclear. This study aimed to characterize choroidal S-nitrosylation and proteomic changes in lens-induced myopia (LIM) to identify SNO-driven regulatory pathways.</div></div><div><h3>Methods</h3><div>Myopia was induced in guinea pigs by unilateral −10 D lens wear (LIM group), with contralateral eyes as normal controls (NC). Ocular changes were assessed by axial length (AL) and refractive error measurements. Choroidal thickness was evaluated via Hematoxylin and Eosin (H&amp;E) staining. Global S-nitrosylation changes were detected by the biotin-switch assay coupled with Western blotting. Integrated proteomic and S-nitrosylomic profiling of choroidal tissues was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatic analyses included functional enrichment analysis and integrative nine-quadrant analysis to identify proteins regulated primarily via S-nitrosylation independent of abundance changes.</div></div><div><h3>Results</h3><div>The LIM model induced significant axial elongation (normalized AL elongation: 0.40 ± 0.68 mm) and a myopic shift (−7.11 ± 1.22 D), accompanied by significant choroidal thinning (49.69 ± 8.67 μm in LIM vs. 70.96 ± 8.90 μm in NC, P = 0.00004). Total choroidal S-nitrosylated protein levels were significantly upregulated in LIM. Integrated dual-omics analysis identified 1293 proteins (corresponding to 1651 modification sites) with significant SNO changes without concomitant protein abundance alterations. Among these, 711 proteins (910 sites) showed upregulated S-nitrosylation in the LIM group. Functional enrichment analysis of these proteins implicated key pathways including Cytoskeleton in muscle cells, Synaptic vesicle cycle, and Ferroptosis. Critical candidates such as HSPG2, FN1, SPTBN1, NSF, and GPX4 were prioritized, suggesting their involvement in extracellular matrix integrity, neurovascular communication, and oxidative stress defense.</div></div><div><h3>Conclusion</h3><div>This study provides the first integrated map of choroidal proteome and S-nitrosylome in myopia, establishing S-nitrosylation as a pivotal post-translational regulatory layer. The data suggest that SNO-mediated dysregulation of cytoskeletal integrity, synaptic signaling, and ferroptosis pathways may contribute to choroidal thinning and dysfunction during myopia progression. These findings nominate specific SNO-modified proteins and their associated pathways as novel potential therapeutic targets for myopia intervention. Future work should focus on the functional validation of the identified SNO sites.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110909"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164704","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":"Uveitis model in rabbit: Dexamethasone loaded PHBSA nanoparticles","authors":"Ebru Erdal ,&nbsp;Barış Batur ,&nbsp;Nagihan Uğurlu ,&nbsp;Esin Akbay Çetin ,&nbsp;Nelisa Laçin Türkoğlu ,&nbsp;Cafer Çakal ,&nbsp;Murat Demirbilek","doi":"10.1016/j.exer.2026.110930","DOIUrl":"10.1016/j.exer.2026.110930","url":null,"abstract":"<div><div>The study aims to investigate the efficacy and safety of intravitreal dexamethasone-loaded polyhydroxybutyrate-stearic acid blend nanoparticles (PHBSA) in treating experimental uveitis. Dexamethasone (DEX) loaded PHBSA nanoparticles were fabricated. An experimental autoimmune uveitis model was established in rabbits and administered the nanoparticles. Fundus fluorescence photometry (FFM), optical coherence tomography (OCT), and fundus examinations were conducted to assess the treatment's effectiveness. Additionally, cytokine levels in the anterior chamber were measured. The uveitis rabbit model was successfully created by the intravitreal injection of 2 μg of lipopolysaccharides (LPS). Following the administration of the DEX-loaded PHBSA nanoparticles, clinical evaluations revealed significant therapeutic effects in both OCT and FFM measurements. A noteworthy change was also observed in the intraocular pressure (IOP) readings. The results indicated a decrease in the clinical signs of uveitis after administering the dexamethasone-loaded nanoparticles, accompanied by a reduction in pro-inflammatory cytokines. These findings suggest that dexamethasone-loaded nanoparticles may serve as a potential treatment for uveitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110930"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193107","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":"Apigenin attenuates LPS-induced corneal inflammation by modulating NF-κB and JNK/ERK signaling pathways","authors":"Jiaqi Lin,&nbsp;Sihao Liu,&nbsp;Xiuping Liu,&nbsp;Jiayi Zheng,&nbsp;Yucheng Wang,&nbsp;Ziyan Chen,&nbsp;Kaili Wu","doi":"10.1016/j.exer.2026.110900","DOIUrl":"10.1016/j.exer.2026.110900","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the protective effects and molecular mechanisms of apigenin (API) on lipopolysaccharide (LPS)-induced corneal inflammation.</div></div><div><h3>Methods</h3><div>Immortalized human corneal epithelial cell line (HCECs) and primary human corneal epithelial cells (PHCECs) were used to establish LPS-induced inflammation models <em>in vitro</em>. IL-6 and IL-8 mRNA and protein levels were assessed by qRT-PCR and ELISA. Transcriptome sequencing and KEGG/GO enrichment analyses were performed to identify key pathways. Western blotting evaluated the activation of MAPK (ERK, JNK, P38) and NF-κB (P65, IκBα) pathway proteins, and immunofluorescence was used to examine P65 nuclear translocation. Furthermore, following the establishment of an inflammation model via intrastromal LPS injection in mice, API was administered to assess its impact on ocular inflammation and pro-inflammatory cytokine expression.</div></div><div><h3>Results</h3><div>API significantly suppressed the expression and secretion of key pro-inflammatory mediators in LPS-stimulated corneal epithelial cells including IL-6, IL-8, and COX2. Transcriptomic analysis confirmed the MAPK and NF-κB pathways as critical components in API'a anti-inflammatory action. API inhibited the phosphorylation of key proteins in the MAPK-JNK/ERK and NF-κB signaling pathways, blocked the nuclear translocation of P65. In mice, API alleviated corneal edema and inflammatory cell infiltration and decreased IL-6 and TNF-α levels in corneal tissue.</div></div><div><h3>Conclusion</h3><div>API effectively attenuates LPS-induced corneal inflammation by inhibiting JNK/ERK and NF-κB signaling pathways and downstream effectors, thereby reducing the production of pro-inflammatory cytokines such as IL-6, IL-8, COX2, and TNF-α.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110900"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131594","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":"Animal-based experimental models in dry eye research: Current approaches and limitations","authors":"Ilayda Korkmaz ,&nbsp;Melis Palamar","doi":"10.1016/j.exer.2026.110918","DOIUrl":"10.1016/j.exer.2026.110918","url":null,"abstract":"<div><div>Experimental animal models offer simplified yet highly controlled systems that enable the systematic exploration of the biological processes underlying human diseases. In dry eye disease (DED), animal models mimic the clinical and pathological features. A wide spectrum of approaches has been developed depending on the targeted mechanism, including aqueous-deficient, evaporative, and mucin-deficient models. Nevertheless, existing models fail to reproduce the multifactorial and heterogeneous nature of DED. Most models are highly useful for short-term evaluations; however, they are insufficient for long-term studies and fail to mimic the chronic course of the disease. Although aqueous-deficient DED models may be advantageous for inducing a more stable and severe DED phenotype, substantial interspecies variability can markedly influence the outcomes. Variability in the lacrimal apparatus, including divided glandular architecture and the presence of accessory glands, such as nictitating membranes and Harderian glands, may attenuate or compensate for the induced phenotype and limit model robustness. Evaporative DED models offer practical advantages and rapid induction but produce only mild ocular surface changes, not reflecting the chronic form of human diseases. A combination of multiple induction methods may yield more comprehensive and physiologically relevant models. In addition to these challenges, the human-oriented design of most diagnostic tests introduces uncertainties in protocol adaptation, optimal thresholds, and interpretation. This review summarizes the key methodologies, diagnostic considerations, advantages, and limitations of the available DED models, while highlighting persistent gaps that constrain their translational relevance.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110918"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178498","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":"Neurotrophin-4 as a promising therapy for corneal injuries: Enhancing epithelial repair and nerve regeneration in abrasion and alkali burn models","authors":"Dai Su ,&nbsp;Qiaoran Qi ,&nbsp;Jin Li ,&nbsp;Xuxiang Zhang","doi":"10.1016/j.exer.2026.110917","DOIUrl":"10.1016/j.exer.2026.110917","url":null,"abstract":"<div><div>Corneal injury and nerve degeneration are complex issues associated with various eye diseases, presenting significant challenges in the field of ophthalmology. Current treatment methods often fail to completely restore corneal nerve function and tissue integrity after injury, underscoring the urgent need for new regenerative strategies. Neurotrophin-4 (NT-4), a member of the neurotrophin family, exerts crucial roles in cell survival and tissue repair through binding to the TrkB receptor. This study investigates the therapeutic potential of NT-4 for corneal injury. In vitro experiments demonstrated that NT-4 enhanced the migration of corneal epithelial cells and axonal outgrowth of trigeminal ganglion cells, effects that were abrogated by the TrkB-specific inhibitor ANA-12. In mouse models, compared to control groups, NT-4 accelerated the healing of both corneal abrasions and alkali burns, elevated corneal nerve density, restored corneal transparency. These findings suggest that NT-4 plays a pivotal role in corneal epithelial repair and sensory nerve regeneration through TrkB-mediated mechanisms, supporting its potential as a therapeutic agent for managing ocular surface injuries.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110917"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178438","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":"Dual-target recombinase polymerase amplification-lateral flow strip (RPA-LFS) for rapid detection of HSV-1 and Fusarium keratoplasticum in infectious keratitis","authors":"Zehua Chen ,&nbsp;Yuting Gu ,&nbsp;Chunyan Xue,&nbsp;Rui Wang,&nbsp;Jie Wu","doi":"10.1016/j.exer.2026.110897","DOIUrl":"10.1016/j.exer.2026.110897","url":null,"abstract":"<div><div>This study focuses on the challenge of pathogen detection in keratitis, aiming to develop a dual target detection strip using recombinant enzyme polymerase amplification (RPA) combined with lateral chromatography strip (LFS) technology, and to detect the specific DNA sequences of Herpes simplex virus type 1 (HSV-1) and <em>Fusarium keratoplasticum (F. keratoplasticum)</em>. To test the detection system in different ocular surface samples for keratitis pathogens diagnosis. The RPA primers with good specificity for HSV-1 and <em>F. keratoplasticum</em> were designed and screened separately, and further modified into probes for a dual target RPA-LFS detection system. This LFS test strip can simultaneously detect HSV-1 and <em>F. keratoplasticum</em>, and distinguish them by the positive bands at different test lines. The detection limit of this test strip for two targets is 203.69 copies/reaction for HSV-1 and 84.91 copies/reaction for <em>F. keratoplasticum</em>. There is no cross reactivity with DNA of other common pathogenic microorganisms of ocular surface except for <em>Candida albicans</em>. In clinical sample testing, the dual target detection system has shown reliable detection performance for both eye swaps and cornea tissue. The dual targets RPA-LFS detection system in this study could be completed within 20 min with visualized results, the coincidence rate with qPCR was 93.3%, indicating its broad clinical application prospects for the clinical diagnosis and treatment of infectious keratitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"266 ","pages":"Article 110897"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131677","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":"2026-04-01","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":"2026-04-01","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}