Background: Age-related macular degeneration (AMD) is a leading cause of vision loss, driven by oxidative stress and inflammation. AMD is reported to be related to oxidative stress and reactive oxygen species (ROS) accumulation resulting from age, smoking and ultraviolet A (UVA) radiation. Phlorizin, a flavonoid with antioxidative and anti-inflammatory properties, has shown potential in mitigating oxidative stress-related conditions, but its role in AMD remains unexplored.

Method: Human ARPE-19 cells were pretreated with phlorizin at varying concentrations (0.01–0.1 μM) and exposed to UVA (20 J/cm²) or NaIO3. Cell viability, ROS generation, MAPK/NF-κB signaling, and pro-inflammatory/pro-angiogenic cytokine expression were analyzed using MTT assays, fluorescence imaging, Western blotting, and RT-qPCR. Color fundus photography (CFP) and fluorescence angiography (FA) analysis were used to examine the effect of phlorizin on choroidal neovascularization (CNV) formation in Laser-induced CNV mouses.

Result: Phlorizin significantly improved cell viability, reduced ROS production, and inhibited MAPK (p38, ERK, JNK) and NF-κB activation in a dose-dependent manner. It also downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-angiogenic factors (VEGF, MMP2, MMP9), demonstrating robust protective effects against oxidative stress and inflammation. CFA and FA revealed that phlorizin pretreatment effectively reduced the FA leakage.

Conclusion: Phlorizin effectively protects ARPE-19 cells from UVA- and NaIO3-induced damage by modulating oxidative and inflammatory pathways. Its antioxidative and anti-inflammatory properties highlight its potential as a therapeutic candidate for AMD prevention and management. Preliminary in vivo study revealed that phlorizin reduced the CNV formation in animal models. Further in vivo studies are warranted to validate these findings.

Keywords：phlorizin, age-related macular degeneration, retinal pigment epithelial cells, MAPK, NF-κB, VEGF, inflammation, oxidative stress