Pub Date : 2026-03-01Epub Date: 2026-01-05DOI: 10.1016/j.exer.2026.110850
Yu-Bo Wu , Yi-Qi Chen , Jian-Bo Mao , Xin Ye , Chen-Xi Wang , Li-Jun Shen
Background
To investigate the relationship between components of internal limiting membrane (ILM) and inner retinal dimples (IRDs) after ILM peeling.
Methods
This study included patients with full-thickness macular hole (FTMH), epiretinal membrane (ERM) and myopic foveoschisis (MF) who underwent pars plana vitrectomy with ILM peeling. The number of IRDs was determined using en face optical coherence tomography (OCT) at 1 month (1 M) and 12 months (12 M) after surgery. The status of Müller cells and the degree of laminin loss were evaluated using the average immunofluorescence intensity and fluorescence area of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4) and laminin (LAMA1) antibodies at peeled ILM. Pearson correlation and multiple linear regression analyses were performed to detect the association between components of ILM and IRDs.
Results
Twelve FTMH cases (12 eyes), 14 MF (14 eyes) cases and 9 ERM cases (9 eyes) were included. Pearson analysis showed that the number of IRDs at 1 M was correlated with the average fluorescence intensity of GFAP (+) (r = −0.440, p = 0.008), area of GFAP (+) (r = −0.640, p < 0.001), and average fluorescence area of LAMA1 (+) (r = 0.600, p = 0.004). IRDs at 12 M was correlated with the average fluorescence area of GFAP (+) (r = −0.706, p < 0.001). Multiple linear regression analysis found that only the average fluorescence area of LAMA1 (+) was significantly correlated with IRDs at 1 M (β = 0.517, 95 % CI: 0.182–0.982, p = 0.007).
Conclusion
The number of postoperative IRDs is correlated with the glial response status of Müller cells at inner retina and the degree of laminin attached with peeled ILM.
{"title":"Immunofluorescence analysis of internal limiting membrane: Insights into formation of inner retinal dimples","authors":"Yu-Bo Wu , Yi-Qi Chen , Jian-Bo Mao , Xin Ye , Chen-Xi Wang , Li-Jun Shen","doi":"10.1016/j.exer.2026.110850","DOIUrl":"10.1016/j.exer.2026.110850","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the relationship between components of internal limiting membrane (ILM) and inner retinal dimples (IRDs) after ILM peeling.</div></div><div><h3>Methods</h3><div>This study included patients with full-thickness macular hole (FTMH), epiretinal membrane (ERM) and myopic foveoschisis (MF) who underwent pars plana vitrectomy with ILM peeling. The number of IRDs was determined using en face optical coherence tomography (OCT) at 1 month (1 M) and 12 months (12 M) after surgery. The status of Müller cells and the degree of laminin loss were evaluated using the average immunofluorescence intensity and fluorescence area of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4) and laminin (LAMA1) antibodies at peeled ILM. Pearson correlation and multiple linear regression analyses were performed to detect the association between components of ILM and IRDs.</div></div><div><h3>Results</h3><div>Twelve FTMH cases (12 eyes), 14 MF (14 eyes) cases and 9 ERM cases (9 eyes) were included. Pearson analysis showed that the number of IRDs at 1 M was correlated with the average fluorescence intensity of GFAP (+) (r = −0.440, p = 0.008), area of GFAP (+) (r = −0.640, p < 0.001), and average fluorescence area of LAMA1 (+) (r = 0.600, p = 0.004). IRDs at 12 M was correlated with the average fluorescence area of GFAP (+) (r = −0.706, p < 0.001). Multiple linear regression analysis found that only the average fluorescence area of LAMA1 (+) was significantly correlated with IRDs at 1 M (β = 0.517, 95 % CI: 0.182–0.982, p = 0.007).</div></div><div><h3>Conclusion</h3><div>The number of postoperative IRDs is correlated with the glial response status of Müller cells at inner retina and the degree of laminin attached with peeled ILM.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110850"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917163","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}
Pub Date : 2026-03-01Epub Date: 2026-01-03DOI: 10.1016/j.exer.2026.110847
Yutian Pu , Chunjing Tao , Barbara K. Pierscionek , Kehao Wang
This study investigates the influence of zonular anchorage position and loading mechanism on lens accommodation using finite element analysis. Axisymmetric models of the lens–zonule–ciliary body complex were developed, incorporating anterior, equatorial, and posterior zonular bundles. Four model variants were generated by varying anchorage position (near the pars plicata or pars plana) and loading mechanism (synchronous or asynchronous). Lens morphology, central optical power (COP) and zonular forces were analysed during simulated accommodation. The synchronous loading mechanism induced greater changes in posterior lens and nuclear radii of curvature and produced a wider range of accommodative change, while the asynchronous mechanism induced higher anterior surface steepening and peak central optical power but a smaller accommodative range. Zonular anchorage position slightly affected outcomes only in models with synchronous loading mechanism such that models with anchorage position near the pars plicata yielded greater changes in COP. A nonlinear relationship between central optical power and zonular force was consistently observed, suggesting an optimal range of zonular tension for maximizing lens performance. These findings indicate that zonular loading mechanism significantly influence lens shape and optical performance.
{"title":"Lens shape change is influenced by zonular anchorage and stretching mechanism","authors":"Yutian Pu , Chunjing Tao , Barbara K. Pierscionek , Kehao Wang","doi":"10.1016/j.exer.2026.110847","DOIUrl":"10.1016/j.exer.2026.110847","url":null,"abstract":"<div><div>This study investigates the influence of zonular anchorage position and loading mechanism on lens accommodation using finite element analysis. Axisymmetric models of the lens–zonule–ciliary body complex were developed, incorporating anterior, equatorial, and posterior zonular bundles. Four model variants were generated by varying anchorage position (near the pars plicata or pars plana) and loading mechanism (synchronous or asynchronous). Lens morphology, central optical power (COP) and zonular forces were analysed during simulated accommodation. The synchronous loading mechanism induced greater changes in posterior lens and nuclear radii of curvature and produced a wider range of accommodative change, while the asynchronous mechanism induced higher anterior surface steepening and peak central optical power but a smaller accommodative range. Zonular anchorage position slightly affected outcomes only in models with synchronous loading mechanism such that models with anchorage position near the pars plicata yielded greater changes in COP. A nonlinear relationship between central optical power and zonular force was consistently observed, suggesting an optimal range of zonular tension for maximizing lens performance. These findings indicate that zonular loading mechanism significantly influence lens shape and optical performance.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110847"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899652","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}
Exposure to blue light significantly threatens retinal health, affecting approximately 73 % of the global population. It impairs vision, lowers the quality of life, and adds to public health challenges. Its treatment is getting difficult due to chronicity, limited drug efficacy, side effects, and ocular barriers that hinder conventional drug delivery. Nanoformulations (NFs) have gained attention as adaptable drug delivery systems (DDSs), offering controlled release and customizable physicochemical characteristics. Their application in ocular therapy has shown promise for targeting both anterior and posterior segments of the eye. By accommodating a broad spectrum of therapeutic agents, these nanocarriers help address the limitations of traditional retinal drug delivery methods and offer potential in mitigating blue light-induced retinal damage. Several NFs have shown significant promise in addressing blue light hazards and the retina-related diseases through various mechanisms. Nano-based formulations offer promising strategies for protecting the retina and treating retinal diseases caused by blue light exposure. Antioxidant-loaded liposomes and hydrogels, such as those containing lutein and zeaxanthin, help reduce oxidative stress. In contrast, curcumin-loaded nanoparticles (Cur-NPs) mitigate inflammation in conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR). Polymeric NPs enable gene-specific silencing of pathogenic targets, and metallic NPs enhance photothermal therapy by selectively destroying abnormal retinal cells. These advanced delivery systems, including protective nanofilms, offer improved bioavailability, targeted delivery, and minimal side effects, making them effective tools in combating retinal damage. This review emphasizes the potential of NFs for advanced drug delivery against blue light-induced retinal hazards, highlighting pharmaceutical and pharmacological findings, recent insights, key challenges, and proposed solutions for a better future.
{"title":"Recent advances of novel nanoformulations combatting blue light hazards in the retina","authors":"Somnath Ghosh , Pritam Parua , Koushik Jana , Shirsa Kumar Ghosh , Abhijit Ghosh , Biplab Debnath , Jitu Halder , Rakesh Kumar Sahoo , Vineet Kumar Rai , Priyanka Dash , Chandan Das , Biswakanth Kar , Goutam Ghosh , Goutam Rath","doi":"10.1016/j.exer.2025.110806","DOIUrl":"10.1016/j.exer.2025.110806","url":null,"abstract":"<div><div>Exposure to blue light significantly threatens retinal health, affecting approximately 73 % of the global population. It impairs vision, lowers the quality of life, and adds to public health challenges. Its treatment is getting difficult due to chronicity, limited drug efficacy, side effects, and ocular barriers that hinder conventional drug delivery. Nanoformulations (NFs) have gained attention as adaptable drug delivery systems (DDSs), offering controlled release and customizable physicochemical characteristics. Their application in ocular therapy has shown promise for targeting both anterior and posterior segments of the eye. By accommodating a broad spectrum of therapeutic agents, these nanocarriers help address the limitations of traditional retinal drug delivery methods and offer potential in mitigating blue light-induced retinal damage. Several NFs have shown significant promise in addressing blue light hazards and the retina-related diseases through various mechanisms. Nano-based formulations offer promising strategies for protecting the retina and treating retinal diseases caused by blue light exposure. Antioxidant-loaded liposomes and hydrogels, such as those containing lutein and zeaxanthin, help reduce oxidative stress. In contrast, curcumin-loaded nanoparticles (Cur-NPs) mitigate inflammation in conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR). Polymeric NPs enable gene-specific silencing of pathogenic targets, and metallic NPs enhance photothermal therapy by selectively destroying abnormal retinal cells. These advanced delivery systems, including protective nanofilms, offer improved bioavailability, targeted delivery, and minimal side effects, making them effective tools in combating retinal damage. This review emphasizes the potential of NFs for advanced drug delivery against blue light-induced retinal hazards, highlighting pharmaceutical and pharmacological findings, recent insights, key challenges, and proposed solutions for a better future.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110806"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801956","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}
Pub Date : 2026-03-01Epub Date: 2025-12-22DOI: 10.1016/j.exer.2025.110823
Wei-Ling Bai , Mei-Jun Wang , Jia-He Gan , Ying Huang , Zi-Han Liu , Cong-Ying Li , Ning-Li Wang , Shi-Ming Li
Emerging evidence suggests a link between circadian rhythm and myopia, with studies showing that retinal-specific knockout of the clock gene Bmal1 induces myopia in mice. This study aims to elucidate the relationship between circadian rhythm disruption (CRD) and myopia, and to investigate the potential mechanisms underlying CRD-mediated myopia development. Three-week-old C57BL/6J mice were entrained to a 12 h light/12 h dark (12L/12D) photoperiod for one week. Mice were then randomly assigned to the 12L/12D control group and the CRD groups. CRD groups were divided into two subgroups: Chronic jet lag (light cycle conditions with an 8 h dark advance every 2–3 days, CJL) and Irregular (light cycle conditions alternating among 16L/8D, 8L/16D and 12L/12D). Refraction and axial length (AL) were measured. Further analysis of pathogenic mechanisms was conducted using RNA sequencing. CRD shifted refraction (control vs Irregular: two weeks: 2.61 ± 0.91 D vs −3.97 ± 1.91 D, P = 0.01; four weeks: 1.64 ± 0.72 D vs −5.3 ± 1.09 D, P < 0.0001; control vs CJL: two weeks: 2.61 ± 0.91 D vs −3.93 ± 1.6 D, P = 0.004; four weeks: 1.64 ± 0.72 D vs −6.2 ± 1.36 D, P < 0.001) and increased AL (four weeks: control vs Irregular, 3.318 ± 0.01 mm vs 3.363 ± 0.008 mm, P = 0.001; control vs CJL, 3.318 ± 0.01 mm vs 3.359 ± 0.008 mm, P = 0.004) towards myopia. RNA-sequencing revealed significant enrichment of genes involved in neurotransmitter signaling pathways, including GABAergic synapses, glutamatergic synapses, dopaminergic synapses and synaptic vesicle cycles. This study indicates that circadian rhythm disruption can induce myopia in mice, with RNA-sequencing supporting the potential role of neurotransmitter signaling pathways.
新出现的证据表明,昼夜节律和近视之间存在联系,研究表明,敲除视网膜特异性时钟基因Bmal1会导致小鼠近视。本研究旨在阐明昼夜节律紊乱(circadian rhythm disruption, CRD)与近视的关系,并探讨CRD介导的近视发展的潜在机制。将3周龄C57BL/6J小鼠置于12小时光照/12小时黑暗(12L/12D)光周期1周。然后将小鼠随机分为12L/12D对照组和CRD组。CRD组分为两个亚组:慢性时差(每2-3天提前8小时黑暗的光周期条件,CJL)和不规则(光周期条件在16L/8D, 8L/16D和12L/12D之间交替)。测量折光和轴向长度(AL)。利用RNA测序进一步分析致病机制。CRD转变折射(控制vs不规则:两周:2.61±0.91 vs -3.97±1.91 D, P = 0.01; 4周:1.64±0.72 vs -5.3±1.09 D, P < 0.0001;控制vs CJL:两周:2.61±0.91 vs -3.93±1.6 D, P = 0.004; 4周:1.64±0.72 vs -6.2±1.36 D, P < 0.001),增加了艾尔(4周:控制和不规则,3.318±0.01毫米和3.363±0.008毫米,P = 0.001;控制vs CJL, 3.318±0.01毫米和3.359±0.008毫米,P = 0.004)对近视。rna测序结果显示,参与gaba能突触、谷氨酸能突触、多巴胺能突触和突触囊泡周期等神经递质信号通路的基因显著富集。这项研究表明,昼夜节律中断可以诱导小鼠近视,rna测序支持神经递质信号通路的潜在作用。
{"title":"Circadian rhythm disruption induces myopia in mice","authors":"Wei-Ling Bai , Mei-Jun Wang , Jia-He Gan , Ying Huang , Zi-Han Liu , Cong-Ying Li , Ning-Li Wang , Shi-Ming Li","doi":"10.1016/j.exer.2025.110823","DOIUrl":"10.1016/j.exer.2025.110823","url":null,"abstract":"<div><div>Emerging evidence suggests a link between circadian rhythm and myopia, with studies showing that retinal-specific knockout of the clock gene <em>Bmal1</em> induces myopia in mice. This study aims to elucidate the relationship between circadian rhythm disruption (CRD) and myopia, and to investigate the potential mechanisms underlying CRD-mediated myopia development. Three-week-old C57BL/6J mice were entrained to a 12 h light/12 h dark (12L/12D) photoperiod for one week. Mice were then randomly assigned to the 12L/12D control group and the CRD groups. CRD groups were divided into two subgroups: Chronic jet lag (light cycle conditions with an 8 h dark advance every 2–3 days, CJL) and Irregular (light cycle conditions alternating among 16L/8D, 8L/16D and 12L/12D). Refraction and axial length (AL) were measured. Further analysis of pathogenic mechanisms was conducted using RNA sequencing. CRD shifted refraction (control vs Irregular: two weeks: 2.61 ± 0.91 D vs −3.97 ± 1.91 D, <em>P</em> = 0.01; four weeks: 1.64 ± 0.72 D vs −5.3 ± 1.09 D, <em>P</em> < 0.0001; control vs CJL: two weeks: 2.61 ± 0.91 D vs −3.93 ± 1.6 D, <em>P</em> = 0.004; four weeks: 1.64 ± 0.72 D vs −6.2 ± 1.36 D, <em>P</em> < 0.001) and increased AL (four weeks: control vs Irregular, 3.318 ± 0.01 mm vs 3.363 ± 0.008 mm, <em>P</em> = 0.001; control vs CJL, 3.318 ± 0.01 mm vs 3.359 ± 0.008 mm, <em>P</em> = 0.004) towards myopia. RNA-sequencing revealed significant enrichment of genes involved in neurotransmitter signaling pathways, including GABAergic synapses, glutamatergic synapses, dopaminergic synapses and synaptic vesicle cycles. This study indicates that circadian rhythm disruption can induce myopia in mice, with RNA-sequencing supporting the potential role of neurotransmitter signaling pathways.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110823"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827110","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}
Autoimmune-associated orbital inflammation refers to the inflammation of orbital tissues resulting from immune system dysregulation. Interleukin-17 (IL-17) plays a critical role in immune defense, tissue repair, inflammation, and tumor progression. Given its immunomodulatory functions, this study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in IL17-related genes contribute to susceptibility and clinical manifestations of orbital autoimmune diseases.
A total of 60 patients with orbital autoimmune disease and 60 healthy controls were recruited. Candidate SNPs in IL17A, IL17F, IL17RA, and IL17RC were selected based on known hotspots, including 500 bp upstream and downstream flanking regions. Associations between SNPs and disease status, as well as clinical features such as pain, diplopia, conjunctival inflammation, and eyelid retraction, were analyzed using chi-square or Fisher's exact tests.
The analysis revealed that rs9791323 in the promoter region of the IL17A gene was significantly associated with disease susceptibility (p = 0.045) but not with specific clinical features. Other SNPs were found to correlate with distinct symptoms: in IL17A, rs3804513 was associated with pain (p = 0.012); rs3819024 and rs2275913 with diplopia (p = 0.007 and 0.028, respectively); and rs8193036 with both diplopia (p = 0.002) and eyelid retraction (p = 0.033). In IL17F, rs9463772 was associated with pain (p = 0.005), while rs4715290 and rs11465530 were linked to eyelid retraction (p = 0.014 and 0.030, respectively). Three SNPs in IL17RA—rs4819553, rs4819958, and rs4819554—were significantly associated with conjunctival inflammation (p = 0.012). The IL17RC SNP rs708567 was also related to eyelid retraction (p = 0.049).
In conclusion, rs9791323 in IL17A may contribute to disease susceptibility, while other IL17-related SNPs appear to influence specific clinical features. These findings highlight the potential role of IL17 gene variants in both the pathogenesis and phenotypic variability of autoimmune-associated orbital inflammation.
{"title":"IL17-related gene polymorphisms associated with orbital inflammatory diseases and their clinical features","authors":"Ding-Ping Chen , Wei-Tzu Lin , Fang-Ping Hsu , Yen-Chang Chu","doi":"10.1016/j.exer.2025.110838","DOIUrl":"10.1016/j.exer.2025.110838","url":null,"abstract":"<div><div>Autoimmune-associated orbital inflammation refers to the inflammation of orbital tissues resulting from immune system dysregulation. Interleukin-17 (IL-17) plays a critical role in immune defense, tissue repair, inflammation, and tumor progression. Given its immunomodulatory functions, this study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in IL17-related genes contribute to susceptibility and clinical manifestations of orbital autoimmune diseases.</div><div>A total of 60 patients with orbital autoimmune disease and 60 healthy controls were recruited. Candidate SNPs in IL17A, IL17F, IL17RA, and IL17RC were selected based on known hotspots, including 500 bp upstream and downstream flanking regions. Associations between SNPs and disease status, as well as clinical features such as pain, diplopia, conjunctival inflammation, and eyelid retraction, were analyzed using chi-square or Fisher's exact tests.</div><div>The analysis revealed that rs9791323 in the promoter region of the IL17A gene was significantly associated with disease susceptibility (p = 0.045) but not with specific clinical features. Other SNPs were found to correlate with distinct symptoms: in IL17A, rs3804513 was associated with pain (p = 0.012); rs3819024 and rs2275913 with diplopia (p = 0.007 and 0.028, respectively); and rs8193036 with both diplopia (p = 0.002) and eyelid retraction (p = 0.033). In IL17F, rs9463772 was associated with pain (p = 0.005), while rs4715290 and rs11465530 were linked to eyelid retraction (p = 0.014 and 0.030, respectively). Three SNPs in IL17RA—rs4819553, rs4819958, and rs4819554—were significantly associated with conjunctival inflammation (p = 0.012). The IL17RC SNP rs708567 was also related to eyelid retraction (p = 0.049).</div><div>In conclusion, rs9791323 in IL17A may contribute to disease susceptibility, while other IL17-related SNPs appear to influence specific clinical features. These findings highlight the potential role of IL17 gene variants in both the pathogenesis and phenotypic variability of autoimmune-associated orbital inflammation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110838"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905632","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}
Tenon's capsule, a surgically accessible and biomechanically robust tissue, may offer a suitable alternative, though its molecular similarity to corneal stroma is underexplored. This study aims to profile and compare the ECM composition of human Tenon's capsule and cornea using high-resolution proteomics.
Methods
Proteomic profiling of human cornea, Tenon's capsule, sclera, and conjunctiva (n = 3 each) was performed using LC-MS/MS, followed by normalization and statistical analysis using MBQN and LIMMA in the R environment. Multivariate analyses, differential expression testing, Gene Ontology and KEGG pathway enrichment, and protein–protein interaction analyses were conducted to assess ECM composition and inter-tissue similarities and differences.
Results
Tenon's capsule exhibited the highest proteomic complexity, with 1429 proteins identified, and 897 proteins were commonly detected across all four ocular tissues. Comparative ECM analysis demonstrated substantial overlap in core structural components between Tenon's capsule and cornea, including collagens, small leucine-rich proteoglycans, glycoproteins, adhesion, and cytoskeletal proteins. Quantitative analysis revealed no significant differences in the abundance of major fibrillar collagens (COL1A1, COL3A1), several glycoproteins (laminins, fibronectin, nidogens, tenascins), adhesion/cytoskeletal proteins (talin, filamin, tubulin), and multiple ECM remodelling enzymes (FGF2, MMP2, MMP3, MMP10, TIMP3). In contrast, specific ECM constituents exhibited significant differential abundance, including COL5A2 (p = 0.02), COL7A1 (p = 0.003), COL11A1 (p = 0.01), keratocan (p = 0.013), and the remodelling-associated proteins TGFβ1 (p = 0.002) and SERPINB2 (p = 0.01), indicating shared ECM architecture with tissue-specific quantitative variation.
Conclusion
Proteomic profiling of Tenon's capsule reveals ECM features compatible with those of the corneal stroma, which motivates further biophysical and functional validation to explore future potential of Tenon's capsule as an abundantly available collagen and ECM resource material that can be used to engineer smarter autologous scaffolds for applications in corneal diseases. These findings provide, for the first time, a valuable proteomic reference using human samples; however, with a limited sample size for exploring ECM-driven mechanisms in ocular repair, fibrosis, and regenerative applications.
{"title":"Proteomic mapping of human Tenon's fascia reveals its biomimetic potential for corneal stromal extracellular matrix reconstruction","authors":"Vineet Joshi , Mohd Salman , Deeksha Prasad , Lakshminarayanan Gowtham , Vikram Krishna , Arun Kumar Raut , Falguni Pati , Vivek Singh , Sayan Basu","doi":"10.1016/j.exer.2025.110836","DOIUrl":"10.1016/j.exer.2025.110836","url":null,"abstract":"<div><h3>Aim</h3><div>Tenon's capsule, a surgically accessible and biomechanically robust tissue, may offer a suitable alternative, though its molecular similarity to corneal stroma is underexplored. This study aims to profile and compare the ECM composition of human Tenon's capsule and cornea using high-resolution proteomics.</div></div><div><h3>Methods</h3><div>Proteomic profiling of human cornea, Tenon's capsule, sclera, and conjunctiva (n = 3 each) was performed using LC-MS/MS, followed by normalization and statistical analysis using MBQN and LIMMA in the R environment. Multivariate analyses, differential expression testing, Gene Ontology and KEGG pathway enrichment, and protein–protein interaction analyses were conducted to assess ECM composition and inter-tissue similarities and differences.</div></div><div><h3>Results</h3><div>Tenon's capsule exhibited the highest proteomic complexity, with 1429 proteins identified, and 897 proteins were commonly detected across all four ocular tissues. Comparative ECM analysis demonstrated substantial overlap in core structural components between Tenon's capsule and cornea, including collagens, small leucine-rich proteoglycans, glycoproteins, adhesion, and cytoskeletal proteins. Quantitative analysis revealed no significant differences in the abundance of major fibrillar collagens (COL1A1, COL3A1), several glycoproteins (laminins, fibronectin, nidogens, tenascins), adhesion/cytoskeletal proteins (talin, filamin, tubulin), and multiple ECM remodelling enzymes (FGF2, MMP2, MMP3, MMP10, TIMP3). In contrast, specific ECM constituents exhibited significant differential abundance, including COL5A2 (p = 0.02), COL7A1 (p = 0.003), COL11A1 (p = 0.01), keratocan (p = 0.013), and the remodelling-associated proteins TGFβ1 (p = 0.002) and SERPINB2 (p = 0.01), indicating shared ECM architecture with tissue-specific quantitative variation.</div></div><div><h3>Conclusion</h3><div>Proteomic profiling of Tenon's capsule reveals ECM features compatible with those of the corneal stroma, which motivates further biophysical and functional validation to explore future potential of Tenon's capsule as an abundantly available collagen and ECM resource material that can be used to engineer smarter autologous scaffolds for applications in corneal diseases. These findings provide, for the first time, a valuable proteomic reference using human samples; however, with a limited sample size for exploring ECM-driven mechanisms in ocular repair, fibrosis, and regenerative applications.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110836"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881901","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}
Pub Date : 2026-03-01Epub Date: 2025-12-18DOI: 10.1016/j.exer.2025.110811
Tianyu Cheng , Pengfei Li , Jiancen Tang , Hongping Cui , Jierui Jia , Lu Wang , Qian Li
DNA oxidative damage of lens epithelium cells (LECs) has been proved to be significantly related to age-related cataract (ARC). DCLRE1A, as a member of the DNA interstrand cross-links pathway, can repair damaged DNA. However, DCLRE1A has not been addressed in maintaining mitochondrial healthy. Our findings demonstrated that DCLRE1A alleviated mtDNA oxidative damage and mitochondrial dysfunction. Besides, the E3 ubiquitin ligase SYVN1 interacts with DCLRE1A and promotes its ubiquitination and degradation. Furthermore, SYVN1 knockdown exacerbated H2O2-induced lens opacity in both ex-vitro rat lenses and ARC mouse. Together, these results underscore the pivotal role of DCLRE1A ubiquitination in modulating mitochondrial homeostasis, offering novel insights into ARC pathogenesis. The E3 ubiquitin ligase SYVN1, related to DNA damage repair, offers a promising avenue for treating cataracts with antioxidative.
{"title":"DCLRE1 downregulated by SYVN1-mediated ubiquitination and degradation, weakening mitochondrial homeostasis protection in ARC formation","authors":"Tianyu Cheng , Pengfei Li , Jiancen Tang , Hongping Cui , Jierui Jia , Lu Wang , Qian Li","doi":"10.1016/j.exer.2025.110811","DOIUrl":"10.1016/j.exer.2025.110811","url":null,"abstract":"<div><div>DNA oxidative damage of lens epithelium cells (LECs) has been proved to be significantly related to age-related cataract (ARC). DCLRE1A, as a member of the DNA interstrand cross-links pathway, can repair damaged DNA. However, DCLRE1A has not been addressed in maintaining mitochondrial healthy. Our findings demonstrated that DCLRE1A alleviated mtDNA oxidative damage and mitochondrial dysfunction. Besides, the E3 ubiquitin ligase SYVN1 interacts with DCLRE1A and promotes its ubiquitination and degradation. Furthermore, SYVN1 knockdown exacerbated H<sub>2</sub>O<sub>2</sub>-induced lens opacity in both ex-vitro rat lenses and ARC mouse. Together, these results underscore the pivotal role of DCLRE1A ubiquitination in modulating mitochondrial homeostasis, offering novel insights into ARC pathogenesis. The E3 ubiquitin ligase SYVN1, related to DNA damage repair, offers a promising avenue for treating cataracts with antioxidative.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110811"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800061","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}
Pub Date : 2026-03-01Epub Date: 2025-12-24DOI: 10.1016/j.exer.2025.110830
Riley Forinash , Sean Staggs , Steven Bassnett , Juan Rodriguez
Zonular fibers are essential for suspending the lens within the eye and, in primates, for transmitting forces generated by the ciliary body to drive ocular accommodation. Despite their biomechanical importance, the response of these fibers to sudden strains, and the molecular basis of their exceptional durability remain poorly understood. This is due, in part, to the absence of tools for studying them in isolation. Here, we present a custom-built, cost-effective apparatus designed to isolate, manipulate, and characterize individual zonular fibers under controlled physical and chemical conditions. The apparatus enables quantification of elastic moduli, stress-relaxation behavior, Poisson's ratio, and response to chemical or enzymatic treatments all from a single fiber, while supporting simultaneous imaging and post-experiment analyses by atomic force microscopy (AFM) or other modalities. We describe the design and calibration of the system, provide protocols for sample mounting and mechanical testing, and introduce accessories for high-resolution imaging and temperature control. Using bovine zonular fibers as a model, we demonstrate the system's ability to capture dynamic responses to enzymatic digestion, including time-resolved degradation kinetics following exposure to α-amylase and trypsin. The modular design, precision, and affordability of the apparatus make it a valuable platform for investigating the mechanics of fine elastic fibers in the eye and beyond, with relevance to connective tissue biology across organ systems.
{"title":"Single zonular fiber extraction and characterization: A platform for biomechanical, biochemical and structural analyses","authors":"Riley Forinash , Sean Staggs , Steven Bassnett , Juan Rodriguez","doi":"10.1016/j.exer.2025.110830","DOIUrl":"10.1016/j.exer.2025.110830","url":null,"abstract":"<div><div>Zonular fibers are essential for suspending the lens within the eye and, in primates, for transmitting forces generated by the ciliary body to drive ocular accommodation. Despite their biomechanical importance, the response of these fibers to sudden strains, and the molecular basis of their exceptional durability remain poorly understood. This is due, in part, to the absence of tools for studying them in isolation. Here, we present a custom-built, cost-effective apparatus designed to isolate, manipulate, and characterize individual zonular fibers under controlled physical and chemical conditions. The apparatus enables quantification of elastic moduli, stress-relaxation behavior, Poisson's ratio, and response to chemical or enzymatic treatments all from a single fiber, while supporting simultaneous imaging and post-experiment analyses by atomic force microscopy (AFM) or other modalities. We describe the design and calibration of the system, provide protocols for sample mounting and mechanical testing, and introduce accessories for high-resolution imaging and temperature control. Using bovine zonular fibers as a model, we demonstrate the system's ability to capture dynamic responses to enzymatic digestion, including time-resolved degradation kinetics following exposure to α-amylase and trypsin. The modular design, precision, and affordability of the apparatus make it a valuable platform for investigating the mechanics of fine elastic fibers in the eye and beyond, with relevance to connective tissue biology across organ systems.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110830"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839125","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}
Pub Date : 2026-03-01Epub Date: 2025-12-29DOI: 10.1016/j.exer.2025.110817
Chunxu Yuan , Shuo Yuan , Karin Dedek
The retinal pigment epithelium (RPE) plays a crucial role in the homeostasis of the vertebrate retina as its tight junctions form the outer blood-retina barrier and regulate the movement of substances between the blood and the neural retina. However, the outer blood-retina barrier breaks down in many degenerative retinal diseases, likely due to oxidative stress. This leads to fluid accumulation and inflammation in the retina. As mouse models are important for studying degenerative retinal diseases, methods to assess the integrity of RPE tight junctions in the mouse are needed. In this study, we established a system to measure the transepithelial electrical resistance (TEER) in mouse RPE using an Ussing chamber. We validated the sensitivity of the TEER measurements by adding oxidative stress-related substances, such as lipopolysaccharide and interleukin-1β, to the apical chamber. We used the same substances, which are known to affect tight junction proteins, to study their effect on the morphological integrity of the hexagonal RPE array in a flat-mount preparation. Antibody stainings for zonula occludens-1, claudin-1, and connexin 43 revealed morphological aberrations with an increased number of abnormal intersections after incubation with interleukin-1β. To further quantify this effect, we devised a new method to measure the angular deviations from the hexagonal RPE cell array. In summary, our results show that TEER and quantitative immunohistochemistry effectively assess the barrier function in mouse RPE and allow analyzing mouse models for retinal degeneration in the future.
{"title":"Assessing the barrier function of the retinal pigment epithelium in adult mice using transepithelial electrical resistance measurements and quantitative immunohistochemistry","authors":"Chunxu Yuan , Shuo Yuan , Karin Dedek","doi":"10.1016/j.exer.2025.110817","DOIUrl":"10.1016/j.exer.2025.110817","url":null,"abstract":"<div><div>The retinal pigment epithelium (RPE) plays a crucial role in the homeostasis of the vertebrate retina as its tight junctions form the outer blood-retina barrier and regulate the movement of substances between the blood and the neural retina. However, the outer blood-retina barrier breaks down in many degenerative retinal diseases, likely due to oxidative stress. This leads to fluid accumulation and inflammation in the retina. As mouse models are important for studying degenerative retinal diseases, methods to assess the integrity of RPE tight junctions in the mouse are needed. In this study, we established a system to measure the transepithelial electrical resistance (TEER) in mouse RPE using an Ussing chamber. We validated the sensitivity of the TEER measurements by adding oxidative stress-related substances, such as lipopolysaccharide and interleukin-1β, to the apical chamber. We used the same substances, which are known to affect tight junction proteins, to study their effect on the morphological integrity of the hexagonal RPE array in a flat-mount preparation. Antibody stainings for zonula occludens-1, claudin-1, and connexin 43 revealed morphological aberrations with an increased number of abnormal intersections after incubation with interleukin-1β. To further quantify this effect, we devised a new method to measure the angular deviations from the hexagonal RPE cell array. In summary, our results show that TEER and quantitative immunohistochemistry effectively assess the barrier function in mouse RPE and allow analyzing mouse models for retinal degeneration in the future.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110817"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877999","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}