Pub Date : 2026-01-05DOI: 10.1016/j.exer.2026.110851
Yakun Wang , Xianyang Liu , Shuhao Zeng , Wenxian Yang , Fan Cao , Shengping Hou
Post-translational modifications (PTMs) encompass the spectrum of chemical covalent alterations that proteins undergo after being synthesized from mRNA. These modifications typically involve the covalent bonding of chemical groups or small protein molecules to the amino acid backbones or side chains. Currently, over 650 types of PTMs have been identified, including significant ones such as phosphorylation, ubiquitination, SUMOylation, methylation, acetylation, glycosylation, among other novel varieties like lactylation. However, a systematic review of PTMs associated with immune-mediated ocular diseases remains conspicuously absent in current literature. To fully understand the role of PTM in immune eye diseases, this review systematically introduces the regulatory mechanisms and functions of several important PTMs. Furthermore, this review also encapsulates the mechanisms of PTMs in several pivotal immune-related ocular conditions, specifically uveitis, age-related macular degeneration (AMD), dry eye disease (DED), and diabetic retinopathy (DR). By integrating current evidence, this work not only clarifies the pathogenic contributions of specific PTMs but also identifies their potential as therapeutic targets. Finally, we discuss future research directions and the challenges of translating PTM-based interventions into clinical practice for ocular immune disorders.
{"title":"The role and mechanism of post-translational modifications (PTMs) in immune-related eye diseases","authors":"Yakun Wang , Xianyang Liu , Shuhao Zeng , Wenxian Yang , Fan Cao , Shengping Hou","doi":"10.1016/j.exer.2026.110851","DOIUrl":"10.1016/j.exer.2026.110851","url":null,"abstract":"<div><div>Post-translational modifications (PTMs) encompass the spectrum of chemical covalent alterations that proteins undergo after being synthesized from mRNA. These modifications typically involve the covalent bonding of chemical groups or small protein molecules to the amino acid backbones or side chains. Currently, over 650 types of PTMs have been identified, including significant ones such as phosphorylation, ubiquitination, SUMOylation, methylation, acetylation, glycosylation, among other novel varieties like lactylation. However, a systematic review of PTMs associated with immune-mediated ocular diseases remains conspicuously absent in current literature. To fully understand the role of PTM in immune eye diseases, this review systematically introduces the regulatory mechanisms and functions of several important PTMs. Furthermore, this review also encapsulates the mechanisms of PTMs in several pivotal immune-related ocular conditions, specifically uveitis, age-related macular degeneration (AMD), dry eye disease (DED), and diabetic retinopathy (DR). By integrating current evidence, this work not only clarifies the pathogenic contributions of specific PTMs but also identifies their potential as therapeutic targets. Finally, we discuss future research directions and the challenges of translating PTM-based interventions into clinical practice for ocular immune disorders.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110851"},"PeriodicalIF":2.7,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917229","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}
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 (1M) and 12 months (12M) 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 1M 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 12M 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 1M (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":"https://doi.org/10.1016/j.exer.2026.110850","url":null,"abstract":"<p><strong>Background: </strong>To investigate the relationship between components of internal limiting membrane (ILM) and inner retinal dimples (IRDs) after ILM peeling.</p><p><strong>Methods: </strong>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 (1M) and 12 months (12M) 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.</p><p><strong>Results: </strong>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 1M 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 12M 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 1M (β=0.517, 95% CI: 0.182-0.982, p=0.007).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110850"},"PeriodicalIF":2.7,"publicationDate":"2026-01-05","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 : 2026-01-05DOI: 10.1016/j.exer.2026.110848
Jingyi Zhu , Linlin Luo , Qian Luo , Qiumei Hu , Lei Yang , Xiao Chen , Jian Ye
The morphological, mechanical, and cellular response of lenses to acute elevation of intraocular pressure (IOP) remained largely unknown. Therefore, we carried out a comprehensive study on the changes of mouse lenses after acute elevation of IOP, and explored the underlying molecular biological mechanism. Acute ocular hypertension was induced in the eye of adult C57BL/6J mice by cannulation of the anterior chamber. Gross morphology and ultrastructure of the lenses were evaluated by the slit lamp, OCT examinations, immunofluorescence staining, immunohistochemistry, and electron microscope, and physical properties were also measured. RNA sequencing analysis was applied to detect relevant transcriptional alterations. We found that subcapsular lens opacities appeared after the IOP spike. The volume, weight, and water content were subsequently decreased. While the lens capsules and LECs attached displayed no significant structural changes after IOP elevation compared with control lenses, the subcapsular cortex was compressed and disorganized. RNA sequencing analysis showed the biological changes of lenses involve various aspects such as cell adhesion and lens fiber remodeling. Lastly, we confirmed that brinzolamide eye drop was able to reduce the AQP1 level, and improve both the transparency and the water content of the lenses after IOP elevation. In conclusion, our study updates the fundamental insight towards the biomechanical response of lenses and their correlation with cataract development, paving the way for further exploration of protection towards lenses after the IOP spike.
{"title":"Mechanical and cellular response of lenses to acute ocular hypertension: Implications of AQP1 regulating water transport and lenses opacification","authors":"Jingyi Zhu , Linlin Luo , Qian Luo , Qiumei Hu , Lei Yang , Xiao Chen , Jian Ye","doi":"10.1016/j.exer.2026.110848","DOIUrl":"10.1016/j.exer.2026.110848","url":null,"abstract":"<div><div>The morphological, mechanical, and cellular response of lenses to acute elevation of intraocular pressure (IOP) remained largely unknown. Therefore, we carried out a comprehensive study on the changes of mouse lenses after acute elevation of IOP, and explored the underlying molecular biological mechanism. Acute ocular hypertension was induced in the eye of adult C57BL/6J mice by cannulation of the anterior chamber. Gross morphology and ultrastructure of the lenses were evaluated by the slit lamp, OCT examinations, immunofluorescence staining, immunohistochemistry, and electron microscope, and physical properties were also measured. RNA sequencing analysis was applied to detect relevant transcriptional alterations. We found that subcapsular lens opacities appeared after the IOP spike. The volume, weight, and water content were subsequently decreased. While the lens capsules and LECs attached displayed no significant structural changes after IOP elevation compared with control lenses, the subcapsular cortex was compressed and disorganized. RNA sequencing analysis showed the biological changes of lenses involve various aspects such as cell adhesion and lens fiber remodeling. Lastly, we confirmed that brinzolamide eye drop was able to reduce the AQP1 level, and improve both the transparency and the water content of the lenses after IOP elevation. In conclusion, our study updates the fundamental insight towards the biomechanical response of lenses and their correlation with cataract development, paving the way for further exploration of protection towards lenses after the IOP spike.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110848"},"PeriodicalIF":2.7,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917223","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 : 2026-01-03DOI: 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":"2026-01-03","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}
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":"2026-01-03","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}
Glaucoma is one of the major causes of irreversible blindness worldwide. The disease is characterized by the progressive loss of retinal ganglion cells (RGCs), and recent evidence supports a key role for oxidative stress in the pathogenesis. In this review, we systematically examine the mechanisms of oxidative stress in the pathogenesis of RGC injury, including impaired mitochondrial function, neuroinflammation, and complement system dysregulation, as well as increased intraocular pressure (IOP). We then evaluate currently available neuroprotective strategies targeting these pathways and highlight in particular direct antioxidant therapies and inhibition of specific enzymes in the oxidative stress pathways. We then discuss recent advances powered by new methods such as single-cell multi-omics. A notable gap exists between encouraging results in preclinical models and less success in clinical trials. This disconnect points to important new directions for future research.
{"title":"Oxidative stress in glaucomatous retinal ganglion cell injury: Mechanisms and neuroprotective strategies","authors":"Yanzhi Xu , Peiyao Yu , Yifan Xie , Junze Yang , Jianbo Wu , Ling Ling , Wei Zhou","doi":"10.1016/j.exer.2025.110837","DOIUrl":"10.1016/j.exer.2025.110837","url":null,"abstract":"<div><div>Glaucoma is one of the major causes of irreversible blindness worldwide. The disease is characterized by the progressive loss of retinal ganglion cells (RGCs), and recent evidence supports a key role for oxidative stress in the pathogenesis. In this review, we systematically examine the mechanisms of oxidative stress in the pathogenesis of RGC injury, including impaired mitochondrial function, neuroinflammation, and complement system dysregulation, as well as increased intraocular pressure (IOP). We then evaluate currently available neuroprotective strategies targeting these pathways and highlight in particular direct antioxidant therapies and inhibition of specific enzymes in the oxidative stress pathways. We then discuss recent advances powered by new methods such as single-cell multi-omics. A notable gap exists between encouraging results in preclinical models and less success in clinical trials. This disconnect points to important new directions for future research.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110837"},"PeriodicalIF":2.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899703","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":"2025-12-30","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 : 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":"2025-12-29","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}
Pub Date : 2025-12-29DOI: 10.1016/j.exer.2025.110835
Jin Liu , Weijin Qian , Li Yang , Tianyi Zhu , Yining Wei , Lianfei Fang , Sijie Fang , Jing Sun , Huifang Zhou
Thyroid eye disease (TED), the most common adult orbital disease, can significantly impair patients' quality of life. Currently, effective diagnostic and predictive models for TED remain limited, making early intervention and personalized treatment for patients challenging. Oxidative stress (OS) plays an important role in pathogenesis of TED, and OS related biomarkers may serve as good candidates for TED prediction. Here, we integrated the peripheral blood bulk-RNA sequencing data and clinical features of 152 TED, 61 health control (HC), and 20 patients with simple Graves’ disease (GD) to identify potential biomarkers. The intersection of TED-HC and TED-GD differentially expressed genes (DEGs) identified 1220 genes strongly correlated with TED. Enrichment analysis showed upregulation of OS-related biological processes in patients with TED. Integration of DEGs, WGCNA results, and OS-related genes identified six genes as candidate biomarkers. Machine learning algorithms suggested three critical candidate genes (KLF2, SELENON, TXNRD1) with high predictive value and were used to construct an oxidative stress-related predictive gene score (OSRPGS). Receiver operating characteristic curve confirmed the predictive value of OSRPGS with an AUC value of 0.733 (TED vs HC) and 0.705 (TED vs GD). Further patient stratification analysis confirmed that the OSRPGS was associated with tear secretion dysfunction. Furthermore, immune infiltration analysis suggested an upregulation of innate immune responses, especially the monocytes/macrophages subtypes, indicating the initiation of OS-related inflammation. Collectively, our study provides a reliable tool for TED prediction and risk assessment based on OS-related biomarkers. OSRPGS may help with the early recognition and intervention in patients with TED.
甲状腺眼病(TED)是成人最常见的眼窝疾病,严重影响患者的生活质量。目前,有效的TED诊断和预测模型仍然有限,这使得患者的早期干预和个性化治疗具有挑战性。氧化应激(Oxidative stress, OS)在TED的发病机制中起重要作用,而氧化应激相关的生物标志物可能是预测TED的良好候选物。在这里,我们整合了152名TED, 61名健康对照(HC)和20名单纯性格雷夫斯病(GD)患者的外周血大体积rna测序数据和临床特征,以确定潜在的生物标志物。TED- hc和TED- gd差异表达基因(DEGs)的交集鉴定出1220个与TED密切相关的基因。富集分析显示,TED患者的os相关生物学过程上调。整合deg、WGCNA结果和os相关基因,鉴定出6个基因作为候选生物标志物。机器学习算法提出了三个具有高预测价值的关键候选基因(KLF2, SELENON, TXNRD1),并用于构建氧化应激相关预测基因评分(OSRPGS)。受试者工作特征曲线证实了OSRPGS的预测价值,其AUC值分别为0.733 (TED vs HC)和0.705 (TED vs GD)。进一步的患者分层分析证实OSRPGS与泪液分泌功能障碍有关。此外,免疫浸润分析表明先天免疫反应上调,特别是单核/巨噬细胞亚型,表明os相关炎症的开始。总之,我们的研究为基于os相关生物标志物的TED预测和风险评估提供了可靠的工具。OSRPGS可能有助于对TED患者的早期识别和干预。
{"title":"A machine learning-based model for the prediction of thyroid eye disease with oxidative stress-related biomarkers","authors":"Jin Liu , Weijin Qian , Li Yang , Tianyi Zhu , Yining Wei , Lianfei Fang , Sijie Fang , Jing Sun , Huifang Zhou","doi":"10.1016/j.exer.2025.110835","DOIUrl":"10.1016/j.exer.2025.110835","url":null,"abstract":"<div><div>Thyroid eye disease (TED), the most common adult orbital disease, can significantly impair patients' quality of life. Currently, effective diagnostic and predictive models for TED remain limited, making early intervention and personalized treatment for patients challenging. Oxidative stress (OS) plays an important role in pathogenesis of TED, and OS related biomarkers may serve as good candidates for TED prediction. Here, we integrated the peripheral blood bulk-RNA sequencing data and clinical features of 152 TED, 61 health control (HC), and 20 patients with simple Graves’ disease (GD) to identify potential biomarkers. The intersection of TED-HC and TED-GD differentially expressed genes (DEGs) identified 1220 genes strongly correlated with TED. Enrichment analysis showed upregulation of OS-related biological processes in patients with TED. Integration of DEGs, WGCNA results, and OS-related genes identified six genes as candidate biomarkers. Machine learning algorithms suggested three critical candidate genes (<em>KLF2, SELENON, TXNRD1</em>) with high predictive value and were used to construct an oxidative stress-related predictive gene score (OSRPGS). Receiver operating characteristic curve confirmed the predictive value of OSRPGS with an AUC value of 0.733 (TED vs HC) and 0.705 (TED vs GD). Further patient stratification analysis confirmed that the OSRPGS was associated with tear secretion dysfunction. Furthermore, immune infiltration analysis suggested an upregulation of innate immune responses, especially the monocytes/macrophages subtypes, indicating the initiation of OS-related inflammation. Collectively, our study provides a reliable tool for TED prediction and risk assessment based on OS-related biomarkers. OSRPGS may help with the early recognition and intervention in patients with TED.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110835"},"PeriodicalIF":2.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862580","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 : 2025-12-29DOI: 10.1016/j.exer.2025.110834
Xinyao Han , Tiexi Wu , Wenyi Si , Lu Zhang , Shiyu Jiang , Suxia Liu , Xuejiao Qin
Tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2/TIPE2) is a critical regulator of immune and inflammatory responses. Although its roles in diabetic retinopathy and choroidal neovascularization have been reported, its influence on the natural state of retina remains unclear. This study investigated whether TIPE2 knockout alone affects retinal structure and function. Wild-type (WT) and TIPE2−/− mice were categorized into juvenile, adult, and late middle-aged groups. Retinal lamellar thickness and blood perfusion across 17 regions were quantified using ultra-widefield swept-source optical coherence tomography and angiography (SS-OCT/OCTA). Generalized estimating equations (GEE) were applied to account for within-eye correlations and to test main effects of genotype and age. Genotype showed a significant main effect on superficial vascular plexus (Svp) perfusion, indicating overall lower Svp perfusion in TIPE2−/− mice, whereas no significant main effects were detected for deep vascular plexus (Dvp) perfusion. TIPE2−/− mice also exhibited reduced total retinal thickness, with the strong genotype-associated thinning observed in the inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL) and outer nuclear layer (ONL). Age exerted smaller effects, showing a significant main effect on total retinal thickness and retinal pigment epithelium (RPE) thickness. Pan-lactylation levels in retinal tissue were assessed by Western Blot and markedly upregulated in adult TIPE2−/− retinas. These findings demonstrate that TIPE2 deficiency was associated with retina hypoperfusion and age-related retinal thinning, suggesting that TIPE2 plays an essential role in preserving the natural state of retina.
{"title":"Age-related alterations in retinal structure and blood perfusion in TIPE2 gene-knockout mice","authors":"Xinyao Han , Tiexi Wu , Wenyi Si , Lu Zhang , Shiyu Jiang , Suxia Liu , Xuejiao Qin","doi":"10.1016/j.exer.2025.110834","DOIUrl":"10.1016/j.exer.2025.110834","url":null,"abstract":"<div><div>Tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2/TIPE2) is a critical regulator of immune and inflammatory responses. Although its roles in diabetic retinopathy and choroidal neovascularization have been reported, its influence on the natural state of retina remains unclear. This study investigated whether TIPE2 knockout alone affects retinal structure and function. Wild-type (WT) and <em>TIPE2</em><sup><em>−/−</em></sup> mice were categorized into juvenile, adult, and late middle-aged groups. Retinal lamellar thickness and blood perfusion across 17 regions were quantified using ultra-widefield swept-source optical coherence tomography and angiography (SS-OCT/OCTA). Generalized estimating equations (GEE) were applied to account for within-eye correlations and to test main effects of genotype and age. Genotype showed a significant main effect on superficial vascular plexus (Svp) perfusion, indicating overall lower Svp perfusion in <em>TIPE2</em><sup><em>−/−</em></sup> mice, whereas no significant main effects were detected for deep vascular plexus (Dvp) perfusion. <em>TIPE2</em><sup><em>−/−</em></sup> mice also exhibited reduced total retinal thickness, with the strong genotype-associated thinning observed in the inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL) and outer nuclear layer (ONL). Age exerted smaller effects, showing a significant main effect on total retinal thickness and retinal pigment epithelium (RPE) thickness. Pan-lactylation levels in retinal tissue were assessed by Western Blot and markedly upregulated in adult <em>TIPE2</em><sup><em>−/−</em></sup> retinas. These findings demonstrate that TIPE2 deficiency was associated with retina hypoperfusion and age-related retinal thinning, suggesting that TIPE2 plays an essential role in preserving the natural state of retina.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110834"},"PeriodicalIF":2.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877963","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}