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ORIGINAL RESEARCH article

Front. Physiol.

Sec. Cell Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1641653

This article is part of the Research TopicRetinal Degenerative Diseases: Processes and Potential TreatmentsView all 9 articles

RARRES1 Attenuates H2O2-Induced RPE Cell Injury and Inhibits Choroidal Neovascularization

Provisionally accepted
Yimeng  LiYimeng LiCaixia  WangCaixia WangTao  DengTao DengXuejing  LiXuejing LiXu  RenhaoXu RenhaoQingli  ShangQingli Shang*
  • Second Hospital of Hebei Medical University, Shijiazhuang, China

The final, formatted version of the article will be published soon.

Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in the elderly, yet its underlying molecular mechanisms remain incompletely understood, and novel biomarkers and therapeutic targets are urgently needed. This study aimed to identify and functionally characterize potential biomarkers and therapeutic candidates for nAMD, with a focus on retinoic acid receptor responder protein 1 (RARRES1). Tandem mass tag (TMT)–based proteomic analysis was performed on aqueous humor samples from patients with nAMD and age-related cataracts. RARRES1 expression was examined in aqueous humor, laser-induced choroidal neovascularization (CNV) model mice, and human ARPE-19 cells exposed to H₂O₂. Functional studies assessed the effects of RARRES1 on oxidative stress, cell death, inflammatory and angiogenic factor expression, and signaling pathways in ARPE-19 cells. Its effects on proliferation, migration, and tube formation were tested in HUVECs. In vivo, a RARRES1-overexpressing AAV2 vector was injected intraocularly into CNV model mice, and lesion size and vascular leakage were evaluated using fundus fluorescein angiography, hematoxylin and eosin staining, and isolectin B-4 fluorescence staining. RARRES1 was significantly reduced in the aqueous humor of nAMD patients, in CNV model mice, and in H₂O₂-treated ARPE-19 cells. Overexpression of RARRES1 in ARPE-19 cells mitigated oxidative stress–induced damage, suppressed inflammatory and angiogenic factor expression, inhibited JNK phosphorylation, and increased Sirtuin 1 and Nrf2 expression. In HUVECs, RARRES1 reduced proliferation, migration, and tube formation. In vivo, intraocular delivery of RARRES1 significantly reduced CNV lesion size and vascular leakage. RARRES1 protects retinal pigment epithelial cells from oxidative stress, inhibits choroidal neovascularization, and modulates inflammatory and angiogenic pathways. These findings identify RARRES1 as a potential biomarker and therapeutic target for nAMD.

Keywords: neovascular age-related macular degeneration, RARRES1, Choroidal Neovascularization, viability, Oxidative Stress

Received: 05 Jun 2025; Accepted: 01 Oct 2025.

Copyright: © 2025 Li, Wang, Deng, Li, Renhao and Shang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Qingli Shang, qinglishang@hebmu.edu.cn

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