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Injectable Multifunctional Hydrogel with Sustained Release of procyanidin C1 for Selective Senolysis to Remodel Ocular Fundus Neovascularization

ABSTRACT: The abnormal vascular growth in ocular fundus neovascularization is driven by senescent cells that evade apoptosis. These cells trigger chronic inflammation by overproducing senescence-associated secretory phenotype (SASP) factors. To address this, we developed PCC1/PHCF-Gel, a novel dual-mode hydrogel platform for long-term procyanidin C1 (PCC1) release. Its high-dose localized delivery targets p16INK4a+ senescent cells for ablation (senolysis), while low-dose sustained release inhibits SASP-mediated inflammation. To investigate the alterations in senescent features of oxygen-induced retinopathy (OIR) when treated with PCC1/PHCF-Gel, we carried out bulk RNA sequencing. Subsequently, utilizing senescence-related gene sets, namely SASP_Literature Curated UP, Fridman_Senescence_UP, and Global_Senescence_2020, we conducted a Set Gene Enrichment Analysis (GSEA). The analysis results served to reconfirm the accumulation of senescence in the OIR model. However, in the case of the PCC1/PHCF-Gel group, a significant negative correlation with senescence-related genes was observed.

ORGANISM(S): Mus musculus

PROVIDER: GSE301407 | GEO | 2025/07/08

REPOSITORIES: GEO

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