Experimental eye research最新文献_第4页

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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引用次数: 0

Prime editing for ocular gene therapy and disease modeling: a narrative review of advances, delivery, and translational readiness 眼部基因治疗和疾病建模的主要编辑：进展，交付和转化准备的叙述性回顾

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-26 DOI: 10.1016/j.exer.2026.110891

Qing Zhang , Yanhui Yang , Xionggao Huang , Junkai Ma , Yajian Duan , Gaoen Ma , Hetian Lei

Prime editing is a versatile “search-and-replace” genome-editing technology that enables precise and flexible genome correction of genetic sequences by reverse-transcribing an RNA template encoded at the 3′ end of a prime editing guide RNA (pegRNA). It supports the introduction of nucleotide substitutions, and insertions or/and deletions (indels) in living cells without requiring double-stranded DNA breaks or exogenous donor templates. Since its introduction in 2019, prime editing has advanced rapidly-from the first-generation prime editor (PE1) to PE7 and other next-generation variants-with editing efficiencies increasing from 0.7 to 5.5 % to more than 50 % in vitro. Optimization strategies including engineering of the Cas9 and reverse transcriptase domains, refinement of pegRNA architecture, recruitment of auxiliary proteins, and modulation of DNA repair pathways have substantially enhanced editing efficiency, product purity, and target scope across diverse cell types and tissues. These developments are particularly relevant to ophthalmology, where many blinding disorders arise from point mutations or small indels ideally suited for prime editing-based correction. Recent work in retinal cells and animal models has demonstrated the growing feasibility of prime editing to treat inherited retinal diseases, modulate pathological angiogenesis, and achieve precise gene repair in post-mitotic photoreceptors and retinal pigment epithelial cells. As delivery vectors and newer PE variants improve, prime editing is a plausible next-generation platform for a wide range of ocular diseases.

引体编辑是一种多功能的“搜索和替换”基因组编辑技术，通过反向转录在引体编辑指导RNA (pegRNA) 3 '端编码的RNA模板，可以精确和灵活地对基因序列进行基因组校正。它支持在活细胞中引入核苷酸替代，插入或/和缺失（indels），而不需要双链DNA断裂或外源供体模板。自2019年推出以来，初始编辑技术发展迅速，从第一代初始编辑器（PE1）到PE7和其他下一代变体，体外编辑效率从0.7%到5.5%提高到50%以上。优化策略包括Cas9和逆转录酶结构域的工程设计、pegRNA结构的细化、辅助蛋白的招募以及DNA修复途径的调节，这些都大大提高了编辑效率、产品纯度以及跨不同细胞类型和组织的靶标范围。这些发展与眼科特别相关，其中许多致盲疾病源于点突变或适合基于初始编辑的校正的小缺陷。最近在视网膜细胞和动物模型上的研究表明，在治疗遗传性视网膜疾病、调节病理性血管生成以及在有丝分裂后光感受器和视网膜色素上皮细胞中实现精确的基因修复方面，启动编辑的可行性越来越大。随着传递载体和更新的PE变体的改进，初始编辑是一个可行的下一代平台，用于广泛的眼部疾病。

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引用次数: 0

BMP2 inhibits myopia progression by upregulating PPARγ in guinea pigs BMP2通过上调豚鼠PPARγ抑制近视进展。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-24 DOI: 10.1016/j.exer.2026.110881

Zhaoying Cai , Zhiyang Wang , Ying Zhu , Na Li , Mo Wang , Bei Du , Ruihua Wei

Myopia is the most prevalent eye disease globally with currently no safe and accessible treatments available. Bone morphogenetic protein 2 (BMP2) is located in multiple eye tissues and is crucial for eye development and differentiation. Nonetheless, the precise roles of BMP2 in myopia still unclear. In this investigation, we observed a marked decrease in scleral BMP2 levels in form-deprivation myopia (FDM) guinea pigs. Subconjunctival injections of exogenous BMP2 recombinant protein could partially counteract the decline in choroidal blood perfusion (ChBP) and myopia development. Subsequent investigations revealed that BMP2 alleviates the myopia-induced reduction in scleral Collagen type I alpha 1 expression and the elevation of scleral hypoxia-inducible factor-1α (HIF-1α) levels. In an in vitro hypoxia model, the inhibition of peroxisome proliferator-activated receptor γ (PPARγ) counteracts the influence of BMP2 on scleral extracellular matrix (ECM) remodeling in human scleral fibroblasts. In conclusion, our findings demonstrate that BMP2 inhibits myopia development and regulates scleral ECM remodeling through the enhancement of PPARγ, highlighting BMP2 as a viable and easily obtainable candidate for myopia management.

近视是全球最普遍的眼病，目前尚无安全、可获得的治疗方法。骨形态发生蛋白2 （Bone morphogenetic protein 2, BMP2）存在于多种眼部组织中，对眼部发育和分化至关重要。尽管如此，BMP2在近视中的确切作用仍不清楚。在这项研究中，我们观察到形态剥夺性近视（FDM）豚鼠巩膜BMP2水平显著下降。结膜下注射外源性BMP2重组蛋白可以部分抵消脉络膜血灌注（ChBP）下降和近视的发展。随后的研究发现，BMP2减轻了近视引起的巩膜I型胶原α 1表达的降低和巩膜缺氧诱导因子-1α (HIF-1α)水平的升高。在体外缺氧模型中，过氧化物酶体增殖物激活受体γ (PPARγ)的抑制抵消了BMP2对人巩膜成纤维细胞巩膜细胞外基质（ECM）重塑的影响。总之，我们的研究结果表明，BMP2通过增强PPARγ抑制近视发展并调节巩膜ECM重塑，强调BMP2是一种可行且易于获得的近视治疗候选者。

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引用次数: 0

Efficacy of InP/ZnSe/ZnS quantum dots with antibiotics in the treatment of multidrug-resistant Pseudomonas aeruginosa keratitis: Preclinical studies InP/ZnSe/ZnS量子点联合抗生素治疗多重耐药铜绿假单胞菌角膜炎的临床前研究

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-24 DOI: 10.1016/j.exer.2026.110890

Oleg V. Shilovskikh , Vyacheslav О. Ponomarev , Victor N. Kazaykin , Konstantin A. Tkachenko , Alexander S. Vokhmintsev , Ilya A. Weinstein

Antibiotic resistance and the development of fundamentally new drugs and approaches for the conservative treatment of bacterial keratitis are among the main challenges of modern ophthalmology. Laboratory and clinical-experimental studies to model and treat infectious keratitis caused by a hospital strain of Pseudomonas aeruginosa (P. aeruginosa) with multiple drug resistance in laboratory animals using colloidal quantum dots (QD) based conjugates with an InP/ZnSe/ZnS core/multilayer shell structure and antibiotics (tobramycin, cefotaxime) were performed. Experimental randomized animal study with 30 New Zealand White laboratory rabbits was conducted. During the modeling and treatment of infectious keratitis, clinical monitoring of laboratory animals was performed, including the assessment of symptom regression over time, photoregistration of the anterior segment with fluorescein staining, and optical coherence tomography. The susceptibility of P. aeruginosa bacteria to antibiotics, and QD conjugates with cefotaxime was assessed in vitro using the disk diffusion method. The penetration of QD into the corneal layers of 18 enucleated pig eyes was studied using fluorescence microscopy. The high anti-infective activity of QD conjugates with antibiotics against an antibiotic-resistant hospital strain of P. aeruginosa was established both in vitro and in vivo. P. aeruginosa bacteria are resistant to cefotaxime in vitro but are susceptible to the QD solutions used in conjugates with an antibiotic. QD conjugates with tobramycin increase the effectiveness of keratitis treatment from 32 ± 2 % to 88 ± 3 % and accelerate the symptom reversal rate compared to standard antibacterial therapy with tobramycin.

抗生素耐药性和开发新的药物和保守治疗细菌性角膜炎的方法是现代眼科的主要挑战之一。采用基于胶体量子点（QD）的InP/ZnSe/ZnS核/多层壳结构偶联物和抗生素（tobramycin，头孢噻肟）对实验室动物多重耐药铜绿假单胞菌（P. aeruginosa）引起的感染性角膜炎进行了实验室和临床实验研究。选用30只新西兰白兔进行实验随机动物研究。在感染性角膜炎的建模和治疗过程中，对实验动物进行了临床监测，包括评估症状随时间的消退，荧光素染色对前段进行光登记，以及光学相干断层扫描。采用纸片扩散法测定铜绿假单胞菌对抗生素的敏感性，以及QD与头孢噻肟的偶联物。用荧光显微镜观察了QD在18只去核猪眼角膜层内的渗透情况。体外和体内均证实了QD与抗生素结合物对铜绿假单胞菌医院耐药菌株具有较高的抗感染活性。P. aeruginosa细菌在体外对头孢噻肟耐药，但对与抗生素偶联物中使用的QD溶液敏感。与妥布霉素标准抗菌治疗相比，QD联合妥布霉素治疗角膜炎的有效率从32±2%提高到88±3%，症状逆转率加快。

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引用次数: 0

Astaxanthin protects retinal Müller cells against high glucose-induced oxidative stress through the sirtuin 1/AMPK/FOXO1 pathway 虾青素通过Sirtuin 1/AMPK/FOXO1通路保护视网膜上皮细胞免受高糖诱导的氧化应激。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-23 DOI: 10.1016/j.exer.2026.110887

Teck Boon Tew , Chang-Hao Yang

Diabetic retinopathy (DR) is characterized by microvascular damage in the retina due to hyperglycemia-induced oxidative stress. The pivotal role of Müller glial cells in DR pathogenesis has gained increasing recognition. Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, plays a crucial role in DR by preventing mitochondrial damage and apoptosis. Astaxanthin has protective effects against various diseases with its antioxidant and anti-inflammatory potency, but its interaction with SIRT1 in DR has not been explored. We hypothesized that astaxanthin alleviates high glucose (HG)-induced oxidative stress in Müller cells by activating SIRT1. To test this, rat retinal Müller cells (rMC-1 cells) were exposed to various concentrations of astaxanthin under HG conditions. The effects of astaxanthin on oxidative stress and glial proliferation were evaluated by immunohistochemistry and Western blotting. The molecular pathway linking astaxanthin to SIRT1 was explored using specific inhibitors and siRNAs. Under HG conditions, astaxanthin effectively reduced reactive oxygen species (ROS) levels, restored glutathione levels, and preserved mitochondrial function in rMC-1 cells. Astaxanthin also inhibited HG-induced glial activation, as indicated by reduced glial fibrillary acidic protein (GFAP) expression. SIRT1 inhibition attenuated these protective effects, suggesting the involvement of the SIRT1 pathway. Additionally, astaxanthin upregulated AMP-activated protein kinase (AMPK), restoring intracellular NAD⁺ levels and enhancing SIRT1 activity. Furthermore, astaxanthin promoted SIRT1-mediated deacetylation of forkhead box O1 (FOXO1), a direct substrate of SIRT1, inhibiting oxidative stress and glial activation. This study provides insights into the molecular mechanisms by which astaxanthin protects against DR by activating the SIRT1/AMPK/FOXO1 pathway.

糖尿病视网膜病变（DR）的特点是由于高血糖诱导的氧化应激导致视网膜微血管损伤。神经胶质细胞在DR发病中的关键作用已得到越来越多的认识。Sirtuin 1 （SIRT1）是一种烟酰胺腺苷二核苷酸（NAD+）依赖的去乙酰化酶，通过防止线粒体损伤和凋亡在DR中起重要作用。虾青素具有抗氧化和抗炎作用，对多种疾病具有保护作用，但其在DR中与SIRT1的相互作用尚未探讨。我们假设虾青素通过激活SIRT1缓解高糖（HG）诱导的 ller细胞氧化应激。为了验证这一点，在HG条件下，将大鼠视网膜下部 ller细胞（rMC-1细胞）暴露于不同浓度的虾青素。采用免疫组织化学和免疫印迹法观察虾青素对氧化应激和胶质细胞增殖的影响。利用特异性抑制剂和sirna探索虾青素与SIRT1的分子通路。HG条件下，虾青素能有效降低rMC-1细胞的活性氧（ROS）水平，恢复谷胱甘肽水平，并保持线粒体功能。虾青素还可以抑制hg诱导的胶质细胞活化，这可以通过降低胶质纤维酸性蛋白（GFAP）的表达来证明。SIRT1抑制减弱了这些保护作用，提示SIRT1通路参与其中。此外，虾青素上调amp活化蛋白激酶（AMPK），恢复细胞内NAD+水平，增强SIRT1活性。此外，虾青素促进了SIRT1介导的叉头盒O1 （FOXO1）的去乙酰化，FOXO1是SIRT1的直接底物，抑制氧化应激和胶质细胞活化。这项研究揭示了虾青素通过激活SIRT1/AMPK/ fox01通路来预防DR的分子机制。

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引用次数: 0

FGF21 protects retinal pigment epithelium from sodium iodate-induced injury: Association with inhibition of ferroptosis and the NRF2/GPX4 pathway FGF21保护视网膜色素上皮免受碘酸钠诱导的损伤：与抑制铁下沉和NRF2/GPX4通路有关

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-22 DOI: 10.1016/j.exer.2026.110883

Wanxin Liu , Lu Wang , Shuang Jiang

Age-related macular degeneration (AMD) is a leading cause of blindness, with retinal pigment epithelium (RPE) cell death representing a central pathological event. Ferroptosis, an iron-dependent form of regulated cell death, has recently been implicated in RPE degeneration. Although fibroblast growth factor 21 (FGF21) has demonstrated cytoprotective effects in various contexts, its specific role and mechanism in RPE protection, particularly concerning ferroptosis, remain unexplored. This study investigated the protective effect of FGF21 against sodium iodate (NaIO3)-induced damage and its underlying mechanism, with a focus on ferroptosis. In vitro, NaIO3 treatment induced significant injury in ARPE-19 cells, which was effectively rescued by FGF21 co-treatment. The protective efficacy of FGF21 was comparable to that of the specific ferroptosis inhibitor Ferrostatin-1. Mechanistically, FGF21 alleviated intracellular iron overload in ARPE-19 cells by modulating the expression of iron regulators (CD71 and FPN1), reduced lipid peroxidation, and restored glutathione levels. Mechanistic exploration revealed that FGF21 treatment was associated with the upregulation of NRF2 and HO-1 and, crucially, with the attenuation of GPX4 downregulation. In a NaIO3-induced mouse model of retinal degeneration, FGF21 administration significantly preserved retinal structure, as evidenced by the maintained outer nuclear layer and total retinal thickness in optical coherence tomography (OCT) and histological analyses. Consistent with the cellular findings, FGF21 upregulated GPX4, NRF2, and HO-1 protein expression in retinal tissues. Our findings demonstrate that FGF21 protects ARPE-19 cells and the retina from NaIO3-induced damage. Its protective profile is closely associated with the mitigation of key ferroptosis hallmarks and correlates with the modulation of the NRF2/GPX4 antioxidant axis. This study provides novel insights and important preclinical evidence supporting further investigation into FGF21 as a potential therapeutic agent for ferroptosis-related retinal degenerative diseases.

年龄相关性黄斑变性（AMD）是失明的主要原因，视网膜色素上皮（RPE）细胞死亡是中心病理事件。铁下垂，一种铁依赖性的调节细胞死亡形式，最近被认为与RPE变性有关。尽管成纤维细胞生长因子21 （FGF21）已在多种情况下显示出细胞保护作用，但其在RPE保护中的具体作用和机制，特别是在铁下垂方面，仍未被探索。本研究探讨了FGF21对碘酸钠（NaIO3）诱导的损伤的保护作用及其潜在机制，重点研究了铁凋亡。在体外，NaIO3处理对ARPE-19细胞造成明显损伤，FGF21联合处理可有效挽救ARPE-19细胞。FGF21的保护作用与特异性铁下垂抑制剂Ferrostatin-1相当。在机制上，FGF21通过调节铁调节因子（CD71和FPN1）的表达，减少脂质过氧化，恢复谷胱甘肽水平，减轻ARPE-19细胞内铁超载。机制探索显示，FGF21处理与NRF2和HO-1的上调有关，关键是与GPX4下调的减弱有关。在naio3诱导的视网膜变性小鼠模型中，FGF21显著保护了视网膜结构，光学相干断层扫描（OCT）和组织学分析显示，外核层和视网膜总厚度得以维持。与细胞结果一致，FGF21上调了视网膜组织中GPX4、NRF2和HO-1蛋白的表达。我们的研究结果表明，FGF21可以保护ARPE-19细胞和视网膜免受naio3诱导的损伤。它的保护特征与减轻关键铁死亡标志密切相关，并与NRF2/GPX4抗氧化轴的调节相关。该研究提供了新的见解和重要的临床前证据，支持进一步研究FGF21作为铁中毒相关视网膜退行性疾病的潜在治疗剂。

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引用次数: 0

Elevated expression of hsa_circ_0053004 in peripheral blood mononuclear cells correlates with endothelial dysfunction in diabetic retinopathy Hsa_circ_0053004在糖尿病视网膜病变患者外周血单核细胞中的表达升高与内皮功能障碍相关

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-21 DOI: 10.1016/j.exer.2026.110880

Xixi Zhang , Jiahui Jiang , Ying Chen , Juntao Zhang , Jinglin Zhu , Zai-Long Chi , Yufei Wu , Qinkang Lu

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and a leading cause of vision loss. Circular RNAs (circRNAs) have emerged as promising biomarkers, yet their role in DR remains unclear. In this study, peripheral blood mononuclear cells (PBMCs) and aqueous humor samples from patients with diabetes mellitus and DR were analyzed by circRNA microarray, with candidate transcripts validated by real-time quantitative PCR. Receiver operating characteristic analysis was performed to assess diagnostic performance. Functional assays using human retinal microvascular endothelial cells (hRMECs), together with bioinformatic prediction and experimental validation, were employed to explore mechanistic pathways. Among the differentially expressed circRNAs, hsa_circ_0053004 was the most significantly upregulated in DR. Its elevated expression was confirmed in both PBMCs and aqueous humor, and gain-of-function studies demonstrated that hsa_circ_0053004 promotes endothelial dysfunction in hRMECs, at least in part through interactions with miR-139-5p and miR-23a-5p. ROC analysis further revealed its strong discriminative capacity between DR and diabetes mellitus. These findings suggest that hsa_circ_0053004 from PBMCs could serve as a potential diagnostic marker for DR and revealed that it is possibly associated with the pathological mechanisms of DR by affecting endothelial dysfunction.

糖尿病视网膜病变（DR）是糖尿病的主要微血管并发症，也是导致视力丧失的主要原因。环状rna （circRNAs）已成为有前景的生物标志物，但它们在DR中的作用尚不清楚。在这项研究中，我们用circRNA芯片分析了糖尿病和DR患者的外周血单个核细胞（PBMCs）和房水样本，并通过实时定量PCR验证了候选转录本。进行受试者工作特征分析以评估诊断表现。利用人视网膜微血管内皮细胞（hRMECs）进行功能分析，结合生物信息学预测和实验验证，探索其机制途径。在差异表达的circRNAs中，hsa_circ_0053004在dr中表达上调最为显著，其表达升高在pbmc和房水中都得到证实，功能获得研究表明，hsa_circ_0053004促进hRMECs的内皮功能障碍，至少部分是通过与miR-139-5p和miR-23a-5p的相互作用。ROC分析进一步显示DR与糖尿病之间有较强的判别能力。这些发现提示pbmc中的hsa_circ_0053004可作为DR的潜在诊断标志物，并揭示其可能通过影响内皮功能障碍与DR的病理机制相关。

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引用次数: 0

Response to letter to the editor, “Significant errors in the paper by Lee R et al.” Ax T. Exp Eye Res. 2025; 263: 110774 对李R等人论文中重大错误的回应[j] .中国医学工程学报，2015;63(3):1107。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-21 DOI: 10.1016/j.exer.2026.110857

Ryung Lee , Joshua Ong , Alex Suh , Mehmet Kadipasaoglu , Thomas Mader , Charles R. Gibson , John Berdahl , Andrew G. Lee , SADES Study Group

引用次数: 0