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The role and mechanism of post-translational modifications (PTMs) in immune-related eye diseases 翻译后修饰(PTMs)在免疫相关眼病中的作用及机制
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-01-05 DOI: 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.
翻译后修饰(PTMs)包括蛋白质从mRNA合成后发生的化学共价改变。这些修饰通常涉及化学基团或小蛋白质分子与氨基酸主干或侧链的共价键。目前,已经鉴定出650多种ptm,包括磷酸化、泛素化、sumo化、甲基化、乙酰化、糖基化等重要的ptm,以及乳酸化等新型ptm。然而,在目前的文献中,ptm与免疫介导的眼部疾病相关的系统综述仍然明显缺失。为了充分了解PTM在免疫性眼病中的作用,本文系统介绍了几种重要的PTM的调控机制和功能。此外,本综述还概述了ptm在几种关键免疫相关眼部疾病中的作用机制,特别是葡萄膜炎、年龄相关性黄斑变性(AMD)、干眼病(DED)和糖尿病视网膜病变(DR)。通过整合现有证据,这项工作不仅阐明了特定ptm的致病作用,而且确定了它们作为治疗靶点的潜力。最后,我们讨论了将基于ptm的干预措施转化为眼免疫疾病临床实践的未来研究方向和挑战。
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引用次数: 0
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 : 2026-01-05 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 (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.

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
Mechanical and cellular response of lenses to acute ocular hypertension: Implications of AQP1 regulating water transport and lenses opacification 晶状体对急性高眼压的机械和细胞反应:AQP1调节水分运输和晶状体混浊的意义。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-01-05 DOI: 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.
晶状体对急性眼内压(IOP)升高的形态学、力学和细胞反应在很大程度上仍然未知。因此,我们对小鼠急性IOP升高后晶状体的变化进行了全面的研究,并探讨了其潜在的分子生物学机制。采用前房插管法诱导成年C57BL/6J小鼠急性高眼压。采用裂隙灯、OCT检查、免疫荧光染色、免疫组织化学、电镜观察观察晶状体的大体形态和超微结构,并测定其物理性质。应用RNA测序分析检测相关转录改变。我们发现晶状体囊下混浊出现在IOP尖峰后。体积、重量和含水量随后下降。与对照晶状体相比,IOP升高后晶状体囊和附着的lec没有明显的结构变化,但囊下皮层被压缩和紊乱。RNA测序分析显示晶状体的生物学变化涉及细胞粘附和晶状体纤维重塑等多个方面。最后,我们证实brinzolamide滴眼液能够降低AQP1水平,提高IOP升高后晶状体的透明度和含水量。总之,我们的研究更新了对晶状体生物力学反应及其与白内障发展相关性的基本认识,为进一步探索IOP尖峰后晶状体的保护铺平了道路。
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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 : 2026-01-03 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
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 : 2026-01-03 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":"2026-01-03","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}
引用次数: 0
Oxidative stress in glaucomatous retinal ganglion cell injury: Mechanisms and neuroprotective strategies 氧化应激在青光眼视网膜神经节细胞损伤中的作用:机制和神经保护策略。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-01-02 DOI: 10.1016/j.exer.2025.110837
Yanzhi Xu , Peiyao Yu , Yifan Xie , Junze Yang , Jianbo Wu , Ling Ling , Wei Zhou
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.
青光眼是世界范围内不可逆失明的主要原因之一。该疾病的特点是视网膜神经节细胞(RGCs)的逐渐丧失,最近的证据支持氧化应激在发病机制中的关键作用。在这篇综述中,我们系统地研究了氧化应激在RGC损伤发病机制中的作用机制,包括线粒体功能受损、神经炎症、补体系统失调以及眼压升高。然后,我们评估了目前针对这些途径的可用神经保护策略,并特别强调了直接抗氧化治疗和氧化应激途径中特定酶的抑制。然后我们讨论了由单细胞多组学等新方法推动的最新进展。在临床前模型中令人鼓舞的结果与在临床试验中不太成功之间存在着显著的差距。这种脱节为未来的研究指明了重要的新方向。
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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 : 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
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 : 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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引用次数: 0
A machine learning-based model for the prediction of thyroid eye disease with oxidative stress-related biomarkers 基于机器学习的氧化应激相关生物标志物甲状腺眼病预测模型
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-12-29 DOI: 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。
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引用次数: 0
Age-related alterations in retinal structure and blood perfusion in TIPE2 gene-knockout mice TIPE2基因敲除小鼠视网膜结构和血液灌注的年龄相关改变。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-12-29 DOI: 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.
肿瘤坏死因子-α-诱导的蛋白8-样2 (TNFAIP8L2/TIPE2)是免疫和炎症反应的关键调节因子。虽然其在糖尿病视网膜病变和脉络膜新生血管中的作用已被报道,但其对视网膜自然状态的影响尚不清楚。本研究探讨单独敲除TIPE2是否会影响视网膜结构和功能。野生型(WT)和TIPE2-/-小鼠分为幼年组、成年组和中老年组。采用超宽视场扫描源光学相干断层扫描和血管造影(SS-OCT/OCTA)对17个区域的视网膜板层厚度和血流灌注进行量化。应用广义估计方程(GEE)来解释眼内相关性,并检验基因型和年龄的主要影响。基因型对TIPE2-/-小鼠的浅血管丛(Svp)灌注有显著的主要影响,表明TIPE2-/-小鼠的Svp灌注总体降低,而对深血管丛(Dvp)灌注无显著的主要影响。TIPE2-/-小鼠也表现出视网膜总厚度的减少,在内核层(INL)、内丛状层(IPL)、外丛状层(OPL)和外核层(ONL)观察到强烈的基因型相关变薄。年龄的影响较小,主要影响视网膜总厚度和视网膜色素上皮(RPE)厚度。Western Blot检测视网膜组织中泛乳酸化水平,发现成人TIPE2-/-视网膜中泛乳酸化水平明显上调。这些发现表明,TIPE2缺乏与视网膜灌注不足和年龄相关性视网膜变薄有关,提示TIPE2在保持视网膜自然状态中起重要作用。
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引用次数: 0
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Experimental eye research
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