Title : Study on the protective effect of RVG29 modified ginsenoside Rg1 liposomes on retinal degeneration
Abstract:
Background: Retinitis pigmentosa (RP), an inherited blinding eye disease, is characterized by the progressive apoptosis of photoreceptors, and clinical therapeutic options remain limited. Ginsenoside Rg1, despite its potentials in antioxidation, anti-apoptosis, and neuroprotection, suffers from poor water solubility and low membrane permeability, which restricts its translational application in ocular treatments. This study focuses on constructing a targeted nano-delivery system to overcome the bottlenecks in drug delivery and explore new strategies for RP treatment.
Methods: RVG29-modified ginsenoside Rg1 gelatin nanoparticles (Rg1@GAR NPs) were constructed. The RVG29 peptide was used to achieve retinal targeting, and gelatin nanoparticles were employed to load the drug (Rg1@Gel NPs). In vitro, the stability, anti-apoptotic activity, and biocompatibility of the nanoparticles were evaluated and the effect of RVG29 modification on retinal photoreceptor cells (661w) was verified. In vivo, using rd10 mice as a model, through electroretinogram (ERG), optical coherence tomography (OCT), and histopathological analysis, the therapeutic mechanism was explored.
Results: Rg1@GAR NPs significantly improved the water solubility and dispersion stability of Rg1. In vitro experiments confirmed that they had anti-apoptotic and endoplasmic reticulum (ER) stress-protective effects on 661w cells. In vivo experiments, the nanoparticles might specifically inhibit the IRE1/XBP1 pathway, reduce ER stress and neuronal apoptosis in the retinas of rd10 mice, improve the structural integrity of the retina and promote the recovery of its function.
Conclusion: Through the synergistic effect of targeted delivery and pathway inhibition, Rg1@GAR NPs provide a novel and potential therapeutic strategy for RP treatment, possess clinical translational value, and are expected to open up a new path for the treatment of hereditary retinal diseases.
