Dual-Target ROS-Driven Spatiotemporal Senolysis for Vascular Repair and Immune Microenvironment Reprogramming in the Treatment of Ocular Fundus Neovascularization.

Yali Zhou, Tianxing Chen, Peiyu Liu, Kangjia Lv, Yifan Wang, Xiaoqian Wang, Junwei Fang, Chong Chen, Zhaoyang Wang, Fang Wei, Xun Xu

Department of Ophthalmology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.Department of Ophthalmology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China. · pubmed

Paper

Abstract

Ocular fundus neovascularization (OFN) is a leading cause of irreversible vision loss. Conventional antivascular endothelial growth factor (anti-VEGF) therapies indiscriminately suppress pathological and reparative angiogenesis and fail to correct the senescence- and inflammation-driven microenvironment that sustains disease progression. Senescent endothelial cells (ECs) form the structural scaffold of pathological vessels, while neighboring senescent microglia exacerbate inflammatory signaling, together deteriorating the reactive oxygen species (ROS)-rich vascular-immune microenvironment. Here, we develop an injectable ROS-responsive senolytic hydrogel (PCC1/PHCF-Gel) that enables lesion-activated, sustained intraocular release of procyanidin C1 (PCC1), overcoming rapid clearance, oxidative degradation, and poor lesion retention associated with free PCC1. In oxygen-induced retinopathy and choroidal neovascularization models, PCC1/PHCF-Gel markedly reduces retinal senescence, suppresses pathological neovascularization, and restores neuroretinal function, outperforming symptom-directed therapies anti-VEGF therapy. Single-cell RNA sequencing reveals selective elimination of two pathogenic senescent cell subpopulations-CXCR4

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that an injectable ROS-responsive senolytic hydrogel can selectively eliminate senescent cells and improve retinal function in models of ocular fundus neovascularization. This research addresses the underlying mechanisms of cellular senescence and inflammation, which are key contributors to aging and age-related diseases, making it relevant to longevity research.

Author of this paper? Send a correction.