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Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
Dual-Target ROS-Driven Spatiotemporal Senolysis for Vascular Repair and Immune Microenvironment Reprogramming in the
Yali Zhou1, Tianxing Chen2, Peiyu Liu1
1Department 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.
A novel hydrogel delivers procyanidin C1 to precisely target and eliminate senescent cells, effectively treating ocular fundus neovascularization and restoring vision. This approach improves upon current therapies by addressing the root causes of disease progression.
Area of Science:
- Ophthalmology
- Biomedical Engineering
- Cell Biology
Background:
- Ocular fundus neovascularization (OFN) causes irreversible vision loss.
- Current anti-VEGF therapies have limitations, failing to address the senescence and inflammation driving OFN.
- Senescent cells, including endothelial cells and microglia, create a detrimental microenvironment.
Purpose of the Study:
- To develop an injectable, ROS-responsive senolytic hydrogel for sustained intraocular delivery of procyanidin C1 (PCC1).
- To evaluate the efficacy of the PCC1/PHCF-Gel in preclinical models of OFN.
- To investigate the mechanism of action, focusing on senescent cell elimination and microenvironment modulation.
Main Methods:
- Development of a ROS-responsive hydrogel (PCC1/PHCF-Gel) for controlled PCC1 release.
- In vivo testing in oxygen-induced retinopathy and choroidal neovascularization models.
- Single-cell RNA sequencing to analyze cellular and molecular changes.
Main Results:
- PCC1/PHCF-Gel demonstrated sustained intraocular release and improved lesion retention compared to free PCC1.
- The treatment significantly reduced retinal senescence, suppressed pathological neovascularization, and restored neuroretinal function.
- Selective elimination of pathogenic senescent CXCR4+ ECs and IFITM3+ microglia was observed, disrupting disease cycles.
Conclusions:
- PCC1/PHCF-Gel represents a promising therapeutic strategy for OFN by targeting senescent cells and modulating the microenvironment.
- This approach offers a multifunctional, spatiotemporally controlled treatment paradigm.
- The findings highlight the potential for precision medicine in treating vision-threatening neovascular diseases.

