Experimental eye research最新文献

{"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}

{"title":"Differential possession of type 6 secretion system effector genes in exoU and exoS Pseudomonas aeruginosa in microbial keratitis","authors":"Tanzina Akter ,&nbsp;Abrar Maswood Haider ,&nbsp;Fiona Stapleton ,&nbsp;Mark Willcox","doi":"10.1016/j.exer.2026.110868","DOIUrl":"10.1016/j.exer.2026.110868","url":null,"abstract":"<div><div>Corneal infection (microbial keratitis; MK) is most frequently caused by <em>Pseudomonas aeruginosa,</em> which can utilize an array of secreted virulence factors for pathogenesis. Invasive strains of <em>P. aeruginosa</em> possessing the <em>exoS</em> gene, invade mammalian cells, while cytotoxic strains with the <em>exoU</em> gene rapidly kill host cells. This study investigated the presence of the type six secretion system (T6SS) effector genes in <em>exoU</em> and <em>exoS</em> strains isolated from MK. Fourteen different T6SS effector genes within 20 <em>exoU</em> and 19 <em>exoS P. aeruginosa</em> were explored using whole genome sequence data by BLAST search. To confirm the BLAST search result, PCR was used to detect <em>exoU, exoS</em> and those genes significantly different in the BLAST search, in a separate set of 56 MK isolates from India (24) and Australia (32). The phospholipase D (PLD) activity was measured using the Amplex Red Phospholipase D Assay kit. Three effector genes, <em>tse7</em>, <em>tle1</em>, and <em>pldA,</em> were differentially possessed in the <em>exoU</em> and <em>exoS</em> strains in the BLAST search (<em>p</em> &lt; 0.05). When combining the BLAST search and PCR results, <em>pldA</em> was significantly more common in <em>exoU</em> (81.8%) than the <em>exoS</em> strains (37.3%) (<em>p</em> &lt; 0.01) and trends were similar in Indian (81% <em>exoU</em> vs 45.5% <em>exoS</em>) and Australian (82.6% <em>exoU</em> vs 23% <em>exoS)</em> isolates. <em>PldA</em> expression was associated with detectable PLD activity. Irrespective of geographical region, <em>pldA</em> was more commonly found in <em>exoU P. aeruginosa.</em> While MK due to <em>exoU</em> is generally more severe than those due to <em>exoS</em>, the association between expression of <em>pldA</em> and its function requires further investigation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110868"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997777","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":"BMP2 inhibits myopia progression by upregulating PPARγ in guinea pigs","authors":"Zhaoying Cai ,&nbsp;Zhiyang Wang ,&nbsp;Ying Zhu ,&nbsp;Na Li ,&nbsp;Mo Wang ,&nbsp;Bei Du ,&nbsp;Ruihua Wei","doi":"10.1016/j.exer.2026.110881","DOIUrl":"10.1016/j.exer.2026.110881","url":null,"abstract":"<div><div>Myopia is the most prevalent eye disease globally with currently no safe and accessible treatments available. Bone morphogenetic protein 2 (BMP2) is located in multiple eye tissues and is crucial for eye development and differentiation. Nonetheless, the precise roles of BMP2 in myopia still unclear. In this investigation, we observed a marked decrease in scleral BMP2 levels in form-deprivation myopia (FDM) guinea pigs. Subconjunctival injections of exogenous BMP2 recombinant protein could partially counteract the decline in choroidal blood perfusion (ChBP) and myopia development. Subsequent investigations revealed that BMP2 alleviates the myopia-induced reduction in scleral Collagen type I alpha 1 expression and the elevation of scleral hypoxia-inducible factor-1α (HIF-1α) levels. In an in vitro hypoxia model, the inhibition of peroxisome proliferator-activated receptor γ (PPARγ) counteracts the influence of BMP2 on scleral extracellular matrix (ECM) remodeling in human scleral fibroblasts. In conclusion, our findings demonstrate that BMP2 inhibits myopia development and regulates scleral ECM remodeling through the enhancement of PPARγ, highlighting BMP2 as a viable and easily obtainable candidate for myopia management.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110881"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050595","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":"2026-04-01","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":"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":"2026-04-01","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}