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Immunofluorescence analysis of internal limiting membrane: Insights into formation of inner retinal dimples 内限定膜的免疫荧光分析:对视网膜内窝形成的见解。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-05 DOI: 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.
背景:探讨内限制膜(ILM)剥脱后各成分与视网膜内窝(IRDs)的关系。方法:对全层黄斑裂孔(FTMH)、视网膜前膜(ERM)、近视视网膜裂孔(MF)患者行玻璃体切割伴ILM剥离术。术后1个月(1M)和12个月(12M)采用面光学相干断层扫描(OCT)测定ird数量。采用去皮ILM时胶质纤维酸性蛋白(GFAP)、水通道蛋白-4 (AQP4)和层粘连蛋白(LAMA1)抗体的平均免疫荧光强度和荧光面积来评价层粘连蛋白缺失程度。采用Pearson相关和多元线性回归分析来检测ILM成分与IRDs之间的相关性。结果:FTMH 12例(12眼),MF 14例(14眼),ERM 9例(9眼)。Pearson分析显示,1M处的IRDs数目与GFAP(+)的平均荧光强度(r=-0.440, p=0.008)、GFAP(+)的面积(r=-0.640, p)相关。结论:术后IRDs数目与视网膜内 ller细胞的胶质反应状态及去皮ILM附着层粘连蛋白的程度相关。
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引用次数: 0
Lens shape change is influenced by zonular anchorage and stretching mechanism 晶状体形态的变化受晶状体带状锚定和拉伸机制的影响。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-03 DOI: 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.
本研究采用有限元分析的方法研究了带状固定位置和加载机制对晶状体调节的影响。建立了晶状体-带状-睫状体复合体的轴对称模型,包括前、赤道和后带状束。通过不同的锚固位置(靠近皱褶部或平面部)和加载机制(同步或异步)产生4种模型变体。在模拟调节过程中,分析了透镜形态、中心光功率(COP)和带状力。同步加载机制诱导晶状体后晶状体和晶状体核曲率半径的变化更大,调节范围更广,而异步加载机制诱导晶状体前表面陡度和中心光功率峰值更高,调节范围更小。带状锚固位置仅在具有同步加载机制的模型中对结果影响较小,锚固位置靠近皱襞部的模型COP变化更大。中心光功率和带状力之间的非线性关系一直被观察到,这表明了一个最佳的带状张力范围,以最大限度地提高透镜的性能。这些结果表明,带状加载机制对透镜形状和光学性能有显著影响。
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引用次数: 0
Recent advances of novel nanoformulations combatting blue light hazards in the retina 对抗视网膜蓝光危害的新型纳米制剂的最新进展
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-19 DOI: 10.1016/j.exer.2025.110806
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
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.
蓝光暴露严重威胁视网膜健康,影响全球约73%的人口。它损害视力,降低生活质量,并增加了公共卫生挑战。由于慢性、有限的药物疗效、副作用和阻碍常规药物传递的眼屏障,其治疗变得越来越困难。纳米制剂(NFs)作为适应性药物传递系统(dds)已经引起了人们的关注,它提供了可控的释放和可定制的物理化学特性。它们在眼部治疗中的应用已经显示出针对眼睛前段和后段的希望。通过适应广泛的治疗药物,这些纳米载体有助于解决传统视网膜药物递送方法的局限性,并提供减轻蓝光引起的视网膜损伤的潜力。一些NFs通过各种机制在解决蓝光危害和视网膜相关疾病方面显示出重大的希望。纳米配方为保护视网膜和治疗蓝光照射引起的视网膜疾病提供了有前途的策略。含有抗氧化剂的脂质体和水凝胶,如含有叶黄素和玉米黄质的脂质体和水凝胶,有助于减少氧化应激。相反,姜黄素纳米颗粒(curcumin- nps)可以减轻年龄相关性黄斑变性(AMD)和糖尿病性视网膜病变(DR)等疾病的炎症。聚合NPs使致病靶点的基因特异性沉默,金属NPs通过选择性破坏异常视网膜细胞来增强光热治疗。这些先进的给药系统,包括保护性纳米膜,提供了更好的生物利用度、靶向给药和最小的副作用,使其成为对抗视网膜损伤的有效工具。这篇综述强调了NFs在对抗蓝光诱导的视网膜危害的高级药物递送方面的潜力,重点介绍了药物和药理学的发现,最近的见解,关键挑战,以及为更好的未来提出的解决方案。
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引用次数: 0
Circadian rhythm disruption induces myopia in mice 昼夜节律紊乱诱导小鼠近视。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 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。
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引用次数: 0
IL17-related gene polymorphisms associated with orbital inflammatory diseases and their clinical features 眼眶炎性疾病相关il17基因多态性及其临床特征
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-03 DOI: 10.1016/j.exer.2025.110838
Ding-Ping Chen , Wei-Tzu Lin , Fang-Ping Hsu , Yen-Chang Chu
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.
自身免疫相关性眼眶炎症是指由免疫系统失调引起的眼眶组织炎症。白细胞介素-17 (IL-17)在免疫防御、组织修复、炎症和肿瘤进展中起着关键作用。鉴于其免疫调节功能,本研究旨在探讨il17相关基因的单核苷酸多态性(snp)是否与眼眶自身免疫性疾病的易感性和临床表现有关。共招募了60名眼眶自身免疫性疾病患者和60名健康对照者。根据已知热点选择IL17A、IL17F、IL17RA和IL17RC的候选snp,包括500 bp的上下游侧翼区域。snp与疾病状态之间的关联,以及诸如疼痛、复视、结膜炎症和眼睑收缩等临床特征,使用卡方检验或Fisher精确检验进行分析。分析显示,IL17A基因启动子区域的rs9791323与疾病易感性显著相关(p = 0.045),但与特定的临床特征无关。其他snp被发现与不同的症状相关:在IL17A中,rs3804513与疼痛相关(p = 0.012);Rs3819024、rs2275913伴复视(p分别= 0.007、0.028);rs8193036同时存在复视(p = 0.002)和眼睑缩回(p = 0.033)。在IL17F中,rs9463772与疼痛相关(p = 0.005),而rs4715290和rs11465530与眼睑缩回相关(p分别= 0.014和0.030)。il17ra中的三个snp -rs4819553、rs4819958和rs4819554-与结膜炎症有显著相关性(p = 0.012)。IL17RC SNP rs708567也与眼睑缩回有关(p = 0.049)。综上所述,IL17A中的rs9791323可能与疾病易感性有关,而其他与il17相关的snp可能影响特定的临床特征。这些发现强调了IL17基因变异在自身免疫相关性眼窝炎症的发病机制和表型变异中的潜在作用。
{"title":"IL17-related gene polymorphisms associated with orbital inflammatory diseases and their clinical features","authors":"Ding-Ping Chen ,&nbsp;Wei-Tzu Lin ,&nbsp;Fang-Ping Hsu ,&nbsp;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}
引用次数: 0
Proteomic mapping of human Tenon's fascia reveals its biomimetic potential for corneal stromal extracellular matrix reconstruction 人类腱膜的蛋白质组学图谱揭示了其在角膜基质细胞外基质重建中的仿生潜力
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-30 DOI: 10.1016/j.exer.2025.110836
Vineet Joshi , Mohd Salman , Deeksha Prasad , Lakshminarayanan Gowtham , Vikram Krishna , Arun Kumar Raut , Falguni Pati , Vivek Singh , Sayan Basu

Aim

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.
AimTenon的胶囊是一种外科手术可及的、生物力学强健的组织,可能是一种合适的替代品,尽管它与角膜基质的分子相似性尚未得到充分研究。本研究旨在利用高分辨率蛋白质组学分析和比较人类Tenon眼膜和角膜的ECM组成。方法采用LC-MS/MS对人角膜、Tenon’s被膜、巩膜和结膜(各3例)进行蛋白质组学分析,并在R环境下采用MBQN和LIMMA进行归一化和统计学分析。通过多变量分析、差异表达检测、基因本体和KEGG通路富集、蛋白相互作用分析来评估ECM组成和组织间异同。结果stenon胶囊的蛋白质组学复杂性最高,鉴定出1429种蛋白质,在所有4种眼部组织中共检测到897种蛋白质。比较ECM分析显示,Tenon’s capsule和角膜之间的核心结构成分存在大量重叠,包括胶原、富含亮氨酸的小蛋白聚糖、糖蛋白、黏附蛋白和细胞骨架蛋白。定量分析显示,主要纤维性胶原蛋白(COL1A1, COL3A1),几种糖蛋白(层粘连蛋白,纤维连接蛋白,nidogens, tenascins),粘附/细胞骨架蛋白(talin, filamin, tubulin)和多种ECM重塑酶(FGF2, MMP2, MMP3, MMP10, TIMP3)的丰度无显著差异。相比而言,特异性ECM成分表现出显著的丰度差异,包括COL5A2 (p = 0.02)、COL7A1 (p = 0.003)、COL11A1 (p = 0.01)、keratocan (p = 0.013)以及重构相关蛋白tgf - β1 (p = 0.002)和SERPINB2 (p = 0.01),表明具有组织特异性定量变异的ECM结构。结论Tenon胶囊的蛋白质组学分析揭示了与角膜基质相容的ECM特征,这将激发进一步的生物物理和功能验证,以探索Tenon胶囊作为丰富的胶原和ECM资源材料的未来潜力,可用于设计更智能的自体支架,用于角膜疾病的应用。这些发现首次为人类样本提供了有价值的蛋白质组学参考;然而,在探索ecm驱动的机制在眼修复、纤维化和再生应用方面的样本量有限。
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引用次数: 0
DCLRE1 downregulated by SYVN1-mediated ubiquitination and degradation, weakening mitochondrial homeostasis protection in ARC formation DCLRE1被syvn1介导的泛素化和降解下调,削弱了ARC形成过程中线粒体稳态保护。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 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.
晶状体上皮细胞(LECs) DNA氧化损伤与老年性白内障(ARC)有显著关系。DCLRE1A作为DNA链间交联通路的一员,可以修复受损的DNA。然而,DCLRE1A在维持线粒体健康方面尚未得到解决。我们的研究结果表明,DCLRE1A减轻了mtDNA氧化损伤和线粒体功能障碍。此外,E3泛素连接酶SYVN1与DCLRE1A相互作用,促进其泛素化和降解。此外,SYVN1敲除加重了h2o2诱导的离体大鼠晶状体和ARC小鼠晶状体混浊。总之,这些结果强调了DCLRE1A泛素化在调节线粒体稳态中的关键作用,为ARC的发病机制提供了新的见解。E3泛素连接酶SYVN1与DNA损伤修复有关,为抗氧化治疗白内障提供了一条有希望的途径。
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引用次数: 0
Single zonular fiber extraction and characterization: A platform for biomechanical, biochemical and structural analyses 单带状纤维提取和表征:生物力学、生化和结构分析的平台
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-24 DOI: 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.
带状纤维对于悬浮眼内晶状体至关重要,在灵长类动物中,用于传递睫状体产生的力以驱动眼部调节。尽管具有重要的生物力学意义,但这些纤维对突然应变的反应,以及其特殊耐久性的分子基础仍然知之甚少。这在一定程度上是由于缺乏单独研究它们的工具。在这里,我们提出了一种定制的,具有成本效益的设备,用于在受控的物理和化学条件下分离,操作和表征单个带状纤维。该仪器可以量化弹性模量、应力松弛行为、泊松比以及对化学或酶处理的反应,所有这些都来自一根纤维,同时支持通过原子力显微镜(AFM)或其他方式进行同步成像和实验后分析。我们描述了该系统的设计和校准,提供了样品安装和机械测试的协议,并介绍了用于高分辨率成像和温度控制的附件。使用牛带状纤维作为模型,我们证明了该系统捕捉酶消化动态响应的能力,包括暴露于α-淀粉酶和胰蛋白酶后的时间分辨降解动力学。该仪器的模块化设计、精度和可负担性使其成为研究眼部及其他部位精细弹性纤维力学的有价值的平台,与跨器官系统的结缔组织生物学相关。
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引用次数: 0
From risk markers to treatable traits in retinal oculomics 从视网膜眼组学的风险标记到可治疗的特征
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-26 DOI: 10.1016/j.exer.2025.110832
Henry Bair
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引用次数: 0
Assessing the barrier function of the retinal pigment epithelium in adult mice using transepithelial electrical resistance measurements and quantitative immunohistochemistry 利用经上皮电阻测量和定量免疫组织化学评估成年小鼠视网膜色素上皮的屏障功能。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-29 DOI: 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.
视网膜色素上皮(RPE)在脊椎动物视网膜的稳态中起着至关重要的作用,因为它的紧密连接形成了外血-视网膜屏障,并调节血液和神经视网膜之间的物质运动。然而,在许多退行性视网膜疾病中,可能由于氧化应激,外血-视网膜屏障被破坏。这会导致视网膜积液和炎症。由于小鼠模型对于研究退行性视网膜疾病非常重要,因此需要评估小鼠RPE紧密连接完整性的方法。在本研究中,我们建立了一个用Ussing室测量小鼠RPE上皮电阻(TEER)的系统。我们通过添加氧化应激相关物质(如脂多糖和白细胞介素-1β)到顶室来验证TEER测量的敏感性。我们使用相同的物质,已知会影响紧密连接蛋白,研究它们对平面安装制备中六边形RPE阵列形态完整性的影响。与白细胞介素-1β孵育后,封闭带-1、claudin-1和连接蛋白43的抗体染色显示形态畸变,异常交叉点数量增加。为了进一步量化这种影响,我们设计了一种新的方法来测量从六边形RPE电池阵列的角度偏差。总之,我们的研究结果表明TEER和定量免疫组织化学有效地评估了小鼠RPE的屏障功能,为将来分析小鼠视网膜变性模型提供了可能。
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Experimental eye research
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