Experimental eye research最新文献

英文中文

Dual-target recombinase polymerase amplification-lateral flow strip (RPA-LFS) for rapid detection of HSV-1 and Fusarium keratoplasticum in infectious keratitis 双靶重组酶聚合酶扩增-横向流动条带（RPA-LFS）快速检测感染性角膜炎HSV-1和角化镰刀菌。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-04 DOI: 10.1016/j.exer.2026.110897

Zehua Chen , Yuting Gu , Chunyan Xue, Rui Wang, Jie Wu

This study focuses on the challenge of pathogen detection in keratitis, aiming to develop a dual target detection strip using recombinant enzyme polymerase amplification (RPA) combined with lateral chromatography strip (LFS) technology, and to detect the specific DNA sequences of Herpes simplex virus type 1 (HSV-1) and Fusarium keratoplasticum (F. keratoplasticum). To test the detection system in different ocular surface samples for keratitis pathogens diagnosis. The RPA primers with good specificity for HSV-1 and F. keratoplasticum were designed and screened separately, and further modified into probes for a dual target RPA-LFS detection system. This LFS test strip can simultaneously detect HSV-1 and F. keratoplasticum, and distinguish them by the positive bands at different test lines. The detection limit of this test strip for two targets is 203.69 copies/reaction for HSV-1 and 84.91 copies/reaction for F. keratoplasticum. There is no cross reactivity with DNA of other common pathogenic microorganisms of ocular surface except for Candida albicans. In clinical sample testing, the dual target detection system has shown reliable detection performance for both eye swaps and cornea tissue. The dual targets RPA-LFS detection system in this study could be completed within 20 min with visualized results, the coincidence rate with qPCR was 93.3%, indicating its broad clinical application prospects for the clinical diagnosis and treatment of infectious keratitis.

本研究针对角膜炎病原体检测面临的挑战，旨在利用重组酶聚合酶扩增（RPA）结合横向色谱条带（LFS）技术开发一种双靶点检测条带，检测单纯疱疹病毒1型（HSV-1）和角化镰刀菌（F. keratoplasticum）的特异性DNA序列。试验检测系统在不同眼表样本中对角膜炎病原菌的诊断价值。分别设计筛选特异性较好的HSV-1和角化F.的RPA引物，并进一步修饰成双靶点RPA- lfs检测系统的探针。该LFS试纸条可同时检测HSV-1和角膜成型F.，并可通过不同检测品系的阳性条带进行区分。该试纸条对1型单纯疱疹病毒的检出限为203.69拷贝/次，对角膜变形F.的检出限为84.91拷贝/次。除白色念珠菌外，与眼表其他常见病原微生物DNA无交叉反应性。在临床样品测试中，双靶标检测系统对换眼和角膜组织均表现出可靠的检测性能。本研究双靶点RPA-LFS检测系统可在20分钟内完成，结果可视化，与qPCR符合率为93.3%，在感染性角膜炎的临床诊断和治疗中具有广阔的临床应用前景。

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引用次数: 0

Predictive value of tear lipidomics biomarkers for TAO activity and relationship with clinical characteristics 泪脂组学标志物对TAO活性的预测价值及其与临床特征的关系。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-03 DOI: 10.1016/j.exer.2026.110901

Xiaofang Wang , Zhiyuan Zhang , Huihui Wu , Yinru Wang , Mengru Su , Xinghong Sun

The objective of this study was to explore the lipid metabolic changes in the active thyroid-associated ophthalmopathy (TAO) through tear lipidomics analysis, screen for biomarkers related to disease activity, and analyze their correlation with clinical features. The study included 32 patients with active TAO and 30 patients with inactive TAO. Liquid chromatography-mass spectrometry (LC-MS) was used to perform lipidomics analysis on tear samples to identify differential lipid molecules. Multivariate statistical analyses, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were conducted, and machine learning algorithms were employed to evaluate the predictive ability of lipid biomarkers. Additionally, clinical characteristics and blood indicators of the patients were collected to analyze their correlation with the lipid biomarkers. The study identified 247 significantly different lipids in the tears of patients with active TAO, of which 104 were upregulated, mainly involving sphingolipids, glycerophospholipids, and glycerolipids. Through machine learning, four lipids (BisMePA(36:6e), MGMG(38:0), PC(38:3), SM(d38:1)) were selected, which showed good predictive ability for TAO activity (AUC >0.8 for all). Moreover, these lipids were significantly correlated with blood lipid indicators, exophthalmos degree, Schirmer I test, and the area of the foveal avascular zone (FAZ) of the retina. This tear lipidomics analysis provides a new approach for screening biomarkers in the active phase of TAO. The identified lipid biomarkers are significantly correlated with clinical features and have potential clinical application value.

本研究旨在通过泪液脂质组学分析，探讨活动性甲状腺相关眼病（TAO）患者的脂质代谢变化，筛选与疾病活动性相关的生物标志物，并分析其与临床特征的相关性。该研究包括32例活动性TAO患者和30例非活动性TAO患者。采用液相色谱-质谱联用（LC-MS）对泪液样品进行脂质组学分析，鉴别不同的脂质分子。进行多元统计分析，包括主成分分析（PCA）和偏最小二乘判别分析（PLS-DA），并采用机器学习算法评估脂质生物标志物的预测能力。收集患者的临床特征和血液指标，分析其与脂质生物标志物的相关性。本研究发现活跃TAO患者泪液中有247种脂质存在显著差异，其中有104种脂质上调，主要涉及鞘脂、甘油磷脂和甘油脂。通过机器学习筛选出4种脂质(BisMePA（36:6e）、MGMG（38:0）、PC（38:3）、SM(d38:1)，对TAO活性具有较好的预测能力（AUC均为>.8）。血脂与血脂指标、眼球突出度、Schirmer I试验、视网膜中央凹无血管区（FAZ）面积有显著相关性。这种泪液脂质组学分析为TAO活动期生物标志物的筛选提供了一种新的方法。所鉴定的脂质生物标志物与临床特征显著相关，具有潜在的临床应用价值。

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引用次数: 0

Topical insulin for corneal wound healing: Interpreting stromal remodeling endpoints 外用胰岛素治疗角膜创面愈合：解释基质重塑终点：回复：“外用胰岛素对角膜创面愈合的再生作用：从表面恢复到基质重塑。”

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-03 DOI: 10.1016/j.exer.2026.110902

Henry Bair

引用次数: 0

PIKfyve is an essential component of the endolysosomal pathway within photoreceptors and the retinal pigment epithelium PIKfyve是光感受器和视网膜色素上皮内溶酶体途径的重要组成部分。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-02-03 DOI: 10.1016/j.exer.2026.110905

Karen Attia , Ifrah Anjum , Susanne Lingrell , Chavy Dworkind , Matthew D. Benson , Ian M. MacDonald , Jennifer C. Hocking

Phosphoinositides (PIs) are a family of seven low abundance membrane lipids, each with distinct signaling functions. The phosphoinositide kinase PIKfyve generates phosphoinositide-3,5-bisphosphate (PI(3,5)P₂) and PI5P. Emerging evidence implicates PIKfyve in key cellular processes, including autophagy, phagocytosis, endosomal trafficking, lysosomal maintenance, and melanosome formation. Complete loss of PIKfyve function is embryonic lethal in model organisms. In humans, heterozygous mutations in PIKFYVE are associated with Fleck corneal dystrophy and congenital cataracts. In this study, we investigate the role of PIKfyve in photoreceptors and the adjacent retinal pigment epithelium (RPE), host to dynamic endolysosomal pathways required for enduring the high oxidative stress environment, transporting metabolites and phototransduction components, and the breakdown of outer segment discs. To assess PIKfyve function in the retina and RPE in our zebrafish model, we employed CRISPR/Cas9-mediated gene editing and pharmacological inhibition using the specific PIKfyve inhibitor apilimod. Loss of PIKfyve activity leads to RPE expansion characterized by the accumulation of LC3- and LAMP1-positive vacuoles, along with defects in phagosome degradation and minor changes to melanosome biogenesis. Photoreceptors deprived of PIKfyve function develop a single large vacuole in the inner segment, while the OS remains largely intact over the timespan analyzed. Electroretinography (ERG) recordings revealed complete visual impairment in pikfyve crispant larvae and significantly reduced visual function in larvae treated with apilimod post embryogenesis. These findings highlight the critical role of PIKfyve in the development and homeostasis of the RPE and retina.

磷酸肌苷（pi）是一个由7个低丰度膜脂组成的家族，每一个都具有不同的信号功能。磷酸肌苷激酶PIKfyve产生磷酸肌苷-3,5-二磷酸（PI(3,5)P2）和PI5P。新出现的证据表明，PIKfyve参与关键的细胞过程，包括自噬、吞噬、内体运输、溶酶体维持和黑素小体的形成。在模式生物中，完全丧失PIKfyve功能是胚胎致命的。在人类中，PIKFYVE的杂合突变与Fleck角膜营养不良和先天性白内障有关。在这项研究中，我们研究了PIKfyve在光感受器和邻近的视网膜色素上皮（RPE）中的作用，RPE是承受高氧化应激环境所需的动态内溶酶体途径的宿主，运输代谢物和光转导成分，以及外节椎间盘的破坏。为了在我们的斑马鱼模型中评估PIKfyve在视网膜和RPE中的功能，我们使用CRISPR/ cas9介导的基因编辑和特异性PIKfyve抑制剂apilimod的药理抑制。PIKfyve活性的丧失导致RPE扩张，其特征是LC3-和lamp1阳性液泡的积累，以及吞噬体降解缺陷和黑素小体生物发生的微小变化。被剥夺PIKfyve功能的光感受器在内节段形成一个大液泡，而在分析的时间范围内，OS基本保持完整。视网膜电图（ERG）记录显示，pikfyve脆化幼虫完全视力受损，胚胎发生后apilimod处理的幼虫视觉功能显著降低。这些发现强调了PIKfyve在RPE和视网膜的发育和稳态中的关键作用。

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引用次数: 0

Proteomic analysis of corneal epithelial cells in patients with neurotrophic keratopathy 神经营养性角膜病变患者角膜上皮细胞的蛋白质组学分析。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-31 DOI: 10.1016/j.exer.2026.110899

Jiarong Luo , Wentao Han , Shaohua Liu , Peiwen Feng , Jiao Tian , Baihua Chen , Shirui Dai , Liwei Zhang

Purpose

This study aimed to identify proteomic differences in the corneal epithelium of Neurotrophic Keratopathy (NK) patients with or without HSV-1 infection compared to normal donors.

Methods

Samples were divided into HSV-1-infected and non-infected NK groups, plus a control group. Corneal epithelial specimens were obtained via curettage/debridement, treated with TMT reagent, and analyzed by HPLC-MS/MS. Differentially expressed proteins underwent GO, KEGG, GSEA, and protein-protein interaction network analyses, with Western blotting validation.

Results

Compared to controls, non-HSV-1 NK patients showed 1228 differentially expressed proteins (771 downregulated, 457 upregulated), while HSV-1-infected NK patients had 939 (617 downregulated, 322 upregulated). Differential proteins play significant roles in many biological processes and pathways, such as epithelial-mesenchymal transition and interferon gamma response. Compared with the control group, there were 569 common differentially expressed proteins in HSV-1 infection and non-infection. We selected the top three upregulated proteins and the downregulated proteins. Their Western blotting results were consistent with the proteomics results.

Conclusion

This study has laid the foundation for the research on the mechanism of NK. It has been discovered that the upregulated (S100A2, TGM1, RPS28) and downregulated (ADH1C, EZH1, CHP2) proteins, which are significantly downregulated in the corneal epithelium of NK patients, may be used as diagnostic markers or therapeutic targets for NK in clinical practice.

目的：本研究旨在确定与正常供体相比，有无HSV-1感染的神经营养性角膜病变（NK）患者角膜上皮蛋白组学差异。方法：将标本分为hsv -1感染NK组和未感染NK组，另加对照组。角膜上皮标本刮除/清创，TMT试剂处理，HPLC-MS/MS分析。差异表达蛋白进行GO、KEGG、GSEA和蛋白相互作用网络分析，并进行Western blot验证。结果：与对照组相比，非hsv -1 NK患者有1228个差异表达蛋白（771个下调，457个上调），而感染hsv -1 NK患者有939个差异表达蛋白（617个下调，322个上调）。差异蛋白在许多生物过程和途径中发挥重要作用，如上皮-间质转化和干扰素γ反应。与对照组比较，1型单纯疱疹病毒感染和未感染组共有差异表达蛋白569个。我们选择了前三个上调蛋白和下调蛋白。他们的Western blotting结果与蛋白质组学结果一致。结论：本研究为NK的机制研究奠定了基础。研究发现，NK患者角膜上皮中显著下调的上调蛋白（S100A2、TGM1、RPS28）和下调蛋白（ADH1C、EZH1、CHP2）可作为NK的诊断标志物或临床治疗靶点。

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引用次数: 0

Re-evaluating “Circadian rhythm disruption induces myopia in mice”: The need to consider sex as a biological variable in translational myopia research 重新评估“昼夜节律中断诱导小鼠近视”：需要考虑性别作为翻译近视研究的生物学变量。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-30 DOI: 10.1016/j.exer.2026.110888

Gang Chen, Yixia Zhang

引用次数: 0

Comment on “Investigation of the biomechanical changes at the iris-lens interface after vitrectomy with silicone oil tamponade: Insights from ultrasound biomicroscopy” 超声生物显微观察玻璃体切除术后虹膜-晶状体界面生物力学变化

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-29 DOI: 10.1016/j.exer.2026.110884

Kanishka Harariya , Thakur Rohit Singh , Ankita Kalra , Swarupanjali Padhi , Fayaz Ahamed

引用次数: 0

Methylome profiling reveals epigenetic alterations in the trabecular meshwork of primary open-angle glaucoma 甲基组分析揭示原发性开角型青光眼小梁网的表观遗传改变。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-27 DOI: 10.1016/j.exer.2026.110892

Ke Liu , Wang-yang Xu , Ruiqing Fu , Yiwen Wang

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. While aberrant DNA methylation may contribute, a genome-wide profile in trabecular meshwork (TM) is lacking. This study performed reduced-representation bisulfite sequencing (RRBS) on TM samples from 42 POAG patients and 20 non-glaucomatous controls, identifying 8885 significant differentially methylated CpG sites (DMCs) and 3148 differentially methylated regions (DMRs), revealing a pronounced hypomethylation pattern in POAG. Hypomethylated genes were associated with ossification, collagen fibril organization, and the RhoA/ROCK signaling, whereas hypermethylated genes were enriched in androgen receptor signaling, the NABA core matrisome, and actin filament processes—collectively highlighting extracellular matrix (ECM) dysregulation as a central theme. Integrated methylome-transcriptome analysis identified four high-priority genes (COL5A1, COL5A2, JAM3, and HTRA1) among hypomethylated-upregulated candidates, implicating them in pathogenic ECM remodeling in POAG. This study presents the first RRBS-based methylome profile of POAG, revealing significant epigenetic alterations in pathways and genes related to TM dysfunction. These findings enhance our understanding of the molecular mechanisms underlying POAG and may inform future therapeutic strategies.

原发性开角型青光眼（POAG）是世界范围内不可逆失明的主要原因。虽然异常DNA甲基化可能起作用，但缺乏小梁网络（TM）的全基因组谱。本研究对42例POAG患者和20例非青光眼对照的TM样本进行了减少代表性亚硫酸盐测序（RRBS），鉴定出8885个显著差异甲基化CpG位点（DMCs）和3148个差异甲基化区域（DMRs），揭示了POAG中明显的低甲基化模式。低甲基化基因与骨化、胶原纤维组织和RhoA/ROCK信号传导相关，而高甲基化基因则富集于雄激素受体信号传导、NABA核心基质体和肌动蛋白丝过程中，共同突出了细胞外基质（ECM）失调作为中心主题。综合甲基组-转录组分析在低甲基化上调的候选基因中发现了四个高优先级基因（COL5A1, COL5A2， JAM3和HTRA1），这表明它们与POAG致病性ECM重塑有关。这项研究首次提出了基于rrbs的POAG甲基化谱，揭示了与TM功能障碍相关的途径和基因的显著表观遗传改变。这些发现增强了我们对POAG分子机制的理解，并可能为未来的治疗策略提供信息。

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引用次数: 0

Axial length prediction Model based on screening fundus photography data in school-age children 基于筛选眼底摄影数据的学龄儿童眼轴长度预测模型。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-27 DOI: 10.1016/j.exer.2026.110893

Zixun Wang , Hua Rong , Jingtao Yu , Yifan Zhou , Xueshuo Xie , Weiping Lin , Zhiqing Li , Hua Yan , Bei Du , Ruihua Wei

This study developed deep learning (DL) models to predict axial length (AL) in 6–10-year-old schoolchildren using minimally abnormal color fundus photographs (CFPs), while evaluating the impact of integrating age, Diopter Sphere (DS), and sex. Following quality assessment of 5460 initial CFPs from 3840 children, 3840 images from 2779 children were utilized and partitioned into training (70 %), validation (20 %), and test (10 %) sets. ResNet101 served as the core architecture, with supplemental clinical parameters integrated into the fully connected layer for continuous AL prediction. Model interpretation employed Grad-CAM-generated heatmaps. Comparative analysis demonstrated that DS and age achieved moderate predictive accuracy (R² = 0.37), a CFP-only model showed significantly stronger performance (R² = 0.70), and combining CFPs with DS and age further improved accuracy (R² = 0.75). However, incorporating sex alongside CFPs, DS, and age substantially reduced efficacy (R² = 0.41). Heatmaps revealed that regions critical for AL predictions anatomically corresponded to retinal vasculature and immediate perivascular tissues. These findings collectively indicate that DL may leverage near-normal CFPs for pediatric AL prediction, with selective enhancement by age and DS, but degradation when categorical variables (such as sex) are included. Subtle changes in the fundus vasculature may help DL to identify the cause of CFP changes with AL.

本研究开发了深度学习（DL）模型，利用最小异常彩色眼底照片（CFPs）预测6-10岁学童的眼轴长度（AL），同时评估综合年龄、屈光度球（DS）和性别的影响。在对来自3,840名儿童的5,460张初始cfp进行质量评估后，使用了来自2,779名儿童的3,840张图像，并将其分为训练集（70%）、验证集（20%）和测试集（10%）。ResNet101作为核心架构，补充临床参数集成到全连接层中，用于连续的人工智能预测。模型解释采用grad - cam生成的热图。对比分析表明，DS和年龄的预测准确率为中等（R2 = 0.37），仅cfp模型的预测准确率显著提高（R2 = 0.70）， cfp与DS和年龄的联合预测准确率进一步提高（R2 = 0.75）。然而，将性别与CFPs、DS和年龄相结合，显著降低了疗效（R2 = 0.41）。热图显示，对AL预测至关重要的区域在解剖学上与视网膜脉管系统和直接血管周围组织相对应。这些研究结果共同表明，DL可以利用接近正常的CFPs来预测儿童AL，年龄和DS有选择性地增强，但当分类变量（如性别）包括在内时，CFPs会下降。眼底脉管系统的细微变化可能有助于DL识别AL伴CFP变化的原因。

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引用次数: 0

N4BP1 promotes the progression of acute glaucoma by promoting pyroptosis through the JAK2/STAT3 pathway N4BP1通过JAK2/STAT3通路促进焦亡，从而促进急性青光眼的进展。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-27 DOI: 10.1016/j.exer.2026.110896

Nan Jiang, Jie Zhu, Jin Zhou, Wensi Chen, Zhenni Zhao, Wenxiang Lin, Ying Yu

Acute glaucoma is the common subtype of glaucoma with unclear mechanism, which is characterized by an abrupt increase in intraocular pressure (IOP) leading to irreversible vision loss. To elucidate the mechanisms underlying the progression of acute glaucoma, here we found that N4BP1, a pivotal regulator innate immune signaling and inflammation, is upregulated in acute glaucoma mice. Notably, knockdown of N4BP1 exhibited alleviation of acute glaucoma symptoms, along with a decrease in microglial activation and pyroptosis levels when compared with the ischemia-reperfusion model group. Subsequently, through the analysis of transcriptome sequencing results, we identified pyroptosis and JAK2/STAT3 as the potential downstream targets of N4BP1. We further confirmed that the JAK2/STAT3 pathway is indeed a critical factor in N4BP1-mediated regulation of microglial activity and pyroptosis levels in vitro. In conclusion, N4BP1 could modulate cell pyroptosis and the progression of acute glaucoma through the JAK2/STAT3 signaling pathway, suggesting its potential as a viable molecular target for the clinical treatment of acute glaucoma in the future.

急性青光眼是青光眼的常见亚型，其发病机制尚不清楚，主要表现为眼压突然升高，导致不可逆的视力丧失。为了阐明急性青光眼发展的机制，我们发现N4BP1，一种关键的先天免疫信号和炎症调节因子，在急性青光眼小鼠中上调。值得注意的是，与缺血-再灌注模型组相比，N4BP1的敲低表现出急性青光眼症状的缓解，以及小胶质细胞激活和焦凋亡水平的降低。随后，通过转录组测序结果分析，我们确定了焦亡和JAK2/STAT3是N4BP1的潜在下游靶点。我们进一步证实JAK2/STAT3通路确实是n4bp1介导的体外小胶质细胞活性和焦亡水平调节的关键因素。综上所述，N4BP1可以通过JAK2/STAT3信号通路调节细胞焦亡和急性青光眼的进展，提示其有可能成为未来临床治疗急性青光眼的可行分子靶点。

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