Experimental eye research最新文献_第4页

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 : 2026-04-01 Epub 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

Extracellular vesicle–mediated delivery of miR-181a-3p confers neuroprotection to degenerating retinal ganglion cells 细胞外囊泡介导的miR-181a-3p传递对变性视网膜神经节细胞具有神经保护作用。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-04-01 Epub Date: 2026-01-21 DOI: 10.1016/j.exer.2026.110882

Esmahan Durmaz , Kubra Trabzonlu , Maryam Esmaeili , Hanady Nehme , Lydia Alverez-Erviti , Yasir Ahmed Syed , Aled Clayton , Ben Mead

Background

Glaucoma is a progressive optic neuropathy marked by the irreversible degeneration of retinal ganglion cells (RGCs), leading to vision loss. RGC injury is also central to other optic and neurodegenerative conditions, including traumatic optic neuropathy.

Purpose

We evaluated whether extracellular vesicles (EVs) derived from retinal precursor cells could serve as an effective platform for the delivery of neuroprotective microRNAs (miRNAs), focusing on miR-181a-3p, to preserve RGC viability and function.

Methods

Based on prior profiling of miRNAs differentially expressed in injured RGCs, four candidate miRNAs were screened for neuroprotective effects in primary rat retinal cultures and human embryonic stem cell–derived RGCs. miR-181a-3p, which showed the strongest preservation of RGC survival, was selected for further study. EVs were isolated from R-28 retinal precursor cells, loaded with miR-181a-3p via electroporation, and characterized for particle size, charge, and loading efficiency. EV uptake and neuroprotective efficacy were evaluated in vitro by fluorescence imaging, qPCR, and Ca²⁺-activity assays, and in vivo by intravitreal injection of labelled EVs to assess retinal distribution and cellular uptake.

Results

EV-mediated delivery of miR-181a-3p enhanced RGC survival and preserved intracellular Ca²⁺ dynamics compared to free miRNA or lipofectamine-based transfection. EVs improved miRNA stability, enabled selective targeting of retinal cell types, and partially modulated the p38/MAPK signalling axis. EV loading also improved the delivery of miRNA to the retina in vivo.

Conclusion

Our findings demonstrate that EVs offer a biocompatible, cell-specific, and functionally effective platform for miRNA delivery to the retina. EV-based administration of miR-181a-3p may represent a novel neuroprotective strategy for glaucoma and related optic neuropathies.

背景：青光眼是一种以视网膜神经节细胞（RGCs）不可逆变性为特征的进行性视神经病变，可导致视力丧失。RGC损伤也是其他视神经退行性疾病的核心，包括外伤性视神经病变。目的：我们评估来自视网膜前体细胞的细胞外囊泡（EVs）是否可以作为传递神经保护性microRNAs （miRNAs）的有效平台，重点是miR-181a-3p，以保持RGC的活力和功能。方法：基于损伤RGCs中差异表达的mirna的先前分析，筛选了四种候选mirna在原代大鼠视网膜培养物和人胚胎干细胞衍生的RGCs中的神经保护作用。我们选择对RGC存活保存能力最强的miR-181a-3p进行进一步研究。从R-28视网膜前体细胞中分离出ev，通过电穿孔负载miR-181a-3p，并对其粒径、电荷和负载效率进行表征。体外通过荧光成像、qPCR和Ca2+活性测定来评估EV的摄取和神经保护功效，体内通过玻璃体内注射标记EV来评估视网膜分布和细胞摄取。结果：与游离miRNA或基于脂质体转染相比，ev介导的miR-181a-3p递送可增强RGC存活并保留细胞内Ca2+动力学。ev提高了miRNA的稳定性，实现了视网膜细胞类型的选择性靶向，并部分调节了p38/MAPK信号轴。EV负载也改善了miRNA向视网膜的体内递送。结论：我们的研究结果表明，ev为miRNA传递到视网膜提供了一个生物相容性、细胞特异性和功能有效的平台。基于ev给药miR-181a-3p可能是青光眼和相关视神经病变的一种新的神经保护策略。

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引用次数: 0

Visual stimulation enhances retrograde transport of BDNF from the superior colliculus to the retina in health and autoimmune uveitis 在健康和自身免疫性葡萄膜炎中，视觉刺激增强BDNF从上丘向视网膜的逆行运输。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.exer.2026.110906

Miloslav Zloh , Patrik Kutilek , Andrea Stofkova

Experimental autoimmune uveoretinitis (EAU) shows degeneration of retinal neurons, including retinal ganglion cells (RGCs), already in its early phase. Based on our previous study demonstrating the attenuation of EAU by brain-derived neurotrophic factor (BDNF), whose retinal levels were increased by visual stimulation (VS), this study evaluated the effect of VS on BDNF protein expression in brain visual centers, its retrograde transport to the retina, and RGC survival in healthy and EAU mice. 14-day VS increased BDNF expression in the superior colliculus (SC) but not in the lateral geniculate nucleus and primary visual cortex in healthy and EAU mice compared to their unstimulated groups. Furthermore, VS increased numbers of BDNF-positive neurons and astrocytes in the retinorecipient superficial SC (sSC) in healthy and EAU mice, although stimulated EAU mice showed a modest reduction in BDNF-positive neurons compared to stimulated healthy mice. In contrast, unstimulated EAU mice exhibited a marked loss of sSC BDNF-positive neurons and astrocytes compared to unstimulated healthy mice. Additionally, VS promoted retrograde axonal transport of fluorescently labeled BDNF from the sSC to the retina, where it was detected in RGCs, inner retinal neurons, and Müller cells (MCs). These results suggest that VS-induced increases in BDNF expression in the sSC and its retrograde transport to the retina may directly affect multiple types of retinal neurons and MCs, on which BDNF can exert neurotrophic and protective effects. The overall attenuation of EAU histopathology and retinal inflammation, along with improved survival of RGCs in VS-treated EAU mice, is consistent with this suggestion.

实验性自身免疫性葡萄膜视网膜炎（EAU）显示视网膜神经元变性，包括视网膜神经节细胞（RGCs），已经处于早期阶段。基于我们之前的研究表明脑源性神经营养因子（BDNF）对EAU的衰减作用，其视网膜水平在视觉刺激（VS）下升高，本研究评估了VS对健康和EAU小鼠脑视觉中心BDNF蛋白表达、向视网膜逆行转运以及RGC存活的影响。与未刺激组相比，14天VS增加了健康小鼠和EAU小鼠上丘（SC）的BDNF表达，但在外侧膝状核和初级视觉皮层中没有。此外，VS增加了健康小鼠和EAU小鼠视网膜受体浅表SC （sSC）中bdnf阳性神经元和星形胶质细胞的数量，尽管与受刺激的健康小鼠相比，受刺激的EAU小鼠显示出bdnf阳性神经元的适度减少。相反，与未刺激的健康小鼠相比，未刺激的EAU小鼠表现出sSC bdnf阳性神经元和星形胶质细胞的明显损失。此外，VS促进了荧光标记的BDNF从sSC向视网膜的轴突逆行运输，在RGCs、视网膜内神经元和突触细胞（MCs）中检测到它。这些结果表明，vs诱导的BDNF在sSC中的表达增加及其向视网膜的逆行转运可能直接影响多种类型的视网膜神经元和MCs， BDNF可对其发挥神经营养和保护作用。在vs治疗的EAU小鼠中，EAU组织病理学和视网膜炎症的总体衰减以及RGCs的生存改善与这一建议一致。

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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 : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1016/j.exer.2026.110902

Henry Bair

引用次数: 0

Duplex droplet digital PCR (ddPCR) improves the diagnosis of Aspergillus and Fusarium keratitis 双液滴数字PCR （ddPCR）提高了曲霉菌和镰刀菌角膜炎的诊断率。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-04-01 Epub Date: 2026-01-17 DOI: 10.1016/j.exer.2026.110866

Yamini Tawde , Sourav Das , Shreya Singh , Soham Basak , Savitri Sharma , Amit Gupta , Amanjit Bal , Shivaprakash M. Rudramurthy , Geetika Yadav , Anup Ghosh

Fungal keratitis (FK) is a serious corneal infection leading to blindness. The present study aims to develop a duplex ddPCR for the detection of Aspergillus sp. and Fusarium sp. causing FK and also to enhance the diagnostic accuracy by evaluating the sensitivity of ddPCR in comparison to qPCR. This Prospective, multicentric study was conducted from November 2019 to August 2021, including three healthcare facilities across India. All patients suspected with FK were included in the study. A part of the collected corneal samples was used for routine microbiological workup and another part of the sample was used for the standardization and validation of ddPCR. A total of 42 corneal buttons were used for standardisation. Aspergillus primer concentration of 750nM showed highest sensitivity of 81.48 % with 93.33 % specificity at ct-value 14.05 while 900 nM primer concentration was best for Fusarium with 80 % sensitivity and 96.3 % specificity at ct-value 83.65. Probe concentrations for both Aspergillus and Fusarium were 250 mM. Validation cohort included 74 corneal samples, Aspergillus ddPCR demonstrated 84.21 % sensitivity with 94.64 % specificity while Fusarium ddPCR had 75 % sensitivity with a specificity of 96.3 %. The comparative analysis demonstrated an improvement in diagnostic performance by ddPCR for both Aspergillus and Fusarium compared to recently reported genus-specific real-time PCR. The ddPCR noticeably enhanced the diagnostic performance for both Aspergillus and Fusarium FK in comparison to the genus-specific real-time PCR. Thus, ddPCR can serve as a rapid technique holding a challenge over conventional and qPCR for FK diagnosis.

真菌性角膜炎是一种严重的角膜感染，可导致失明。本研究旨在建立双链ddPCR检测引起FK的曲霉和镰刀菌，并通过比较ddPCR与qPCR的敏感性来提高诊断的准确性。这项前瞻性多中心研究于2019年11月至2021年8月进行，包括印度各地的三家医疗机构。所有疑似FK患者均纳入研究。收集的一部分角膜样本用于常规微生物检查，另一部分样本用于ddPCR的标准化和验证。共使用42个角膜扣进行标准化。曲霉引物浓度为750 nM时灵敏度最高，为81.48%，特异性为93.33%，ct值为14.05；镰刀菌引物浓度为900 nM时灵敏度最高，为80%，特异性为96.3%，ct值为83.65。曲霉和镰刀菌的探针浓度均为250mM。验证队列包括74份角膜样本，曲霉ddPCR敏感性为84.21%，特异性为94.64%；镰刀菌ddPCR敏感性为75%，特异性为96.3%。对比分析表明，与最近报道的属特异性实时PCR相比，ddPCR对曲霉和镰刀菌的诊断性能有所提高。与属特异性实时PCR相比，ddPCR显著提高了曲霉和镰刀菌FK的诊断性能。因此，ddPCR可以作为一种快速的技术，对传统和qPCR进行FK诊断。

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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 : 2026-04-01 Epub 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

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 : 2026-04-01 Epub 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

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 : 2026-04-01 Epub 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

Resveratrol alleviated diabetic retinal neuronal ferroptosis induced by high glucose through inhibiting HIF-1α and HMOX1 pathway 白藜芦醇通过抑制HIF-1α和HMOX1通路减轻高糖诱导的糖尿病视网膜神经元铁下垂。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-04-01 Epub Date: 2026-01-17 DOI: 10.1016/j.exer.2026.110872

Meng Ye , Yan Jiang , Hongya Gong , Chaowu Wu , Tao Li , Xuhui Chen

Diabetic retinopathy (DR) is a common complication of diabetes mellitus that can cause blindness and affect the life quality of patients. Diabetic retinal neurodegeneration (DRN) caused by high glucose might be the earlier pathological change preceding vascular injury. Resveratrol has been showed to have therapeutic effects on DRN but the mechanism remains unclear. Ferroptosis is a new form of regulated cell death and has been found to be involved in DRN. In this study, we found genetic relationship between resveratrol and ferroptosis in DRN pathogenesis using bioinformatics analysis and demonstrated HIF-1α and HMOX1 as the hub genes. Our study established in vitro model of DRN in high-glucose cultured SH-SY5Y cells and found ferroptosis processes characterized of reactive oxygen species (ROS) accumulation and cellular mitochondrial damage along with upregulation of HIF-1α and HMOX1. Application of resveratrol alleviated high glucose-induced ferroptosis phenotypes in SH-SY5Y cells through inhibiting HIF-1α and HMOX1. We also confirmed ferroptosis process and RGC damage in diabetic (db/db) mouse model. The upregulation of HIF-1α and HMOX1 was also found in diabetic mouse retina. By resveratrol gavage, RGC damage in diabetic (db/db) mouse model was alleviated and the expression level of HIF-1α and HMOX1 in retina was decreased. Our study revealed the involvement of ferroptosis process in retinal neurodegeneration and might provide new insights into neuroprotective interventions in diabetic retinopathy.

糖尿病视网膜病变（DR）是糖尿病常见的并发症，可导致失明，影响患者的生活质量。糖尿病性视网膜神经变性（DRN）可能是血管损伤前的早期病变。白藜芦醇已被证明对DRN有治疗作用，但其机制尚不清楚。铁下垂是一种新的受调控的细胞死亡形式，已被发现与DRN有关。本研究通过生物信息学分析发现了白藜芦醇与DRN发病机制中铁ptosis的遗传关系，并证实HIF-1α和HMOX1为中心基因。我们在高糖培养的SH-SY5Y细胞中建立了DRN体外模型，发现了以活性氧（ROS）积累和细胞线粒体损伤为特征的铁死亡过程，并伴有HIF-1α和HMOX1的上调。白藜芦醇通过抑制HIF-1α和HMOX1减轻高糖诱导的SH-SY5Y细胞铁下垂表型。我们还证实了糖尿病小鼠（db/db）模型的铁下垂过程和RGC损伤。HIF-1α和HMOX1在糖尿病小鼠视网膜中表达上调。白藜芦醇灌胃可减轻糖尿病小鼠RGC损伤（db/db），降低视网膜HIF-1α和HMOX1的表达水平。我们的研究揭示了铁下垂过程参与视网膜神经变性，并可能为糖尿病视网膜病变的神经保护干预提供新的见解。

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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 : 2026-04-01 Epub 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