Microglia’s Roles in AMD to Inform Therapies for Vision Loss Prevention

This project aims to define the roles of specific microglia subtypes in age-related macular degeneration (AMD) models to guide the development of therapies that prevent vision loss.

Outer retinal diseases, like AMD, cause permanent vision loss due to damage to light-sensitive cells. While some immune cells help clear harmful debris, recent findings suggest distinct subtypes with different functions. Genetic analysis identified two subtypes in a certain immune cell, one of which may worsen inflammation. Studies with genetically modified mice showed that reducing certain molecules in these cells reduced retinal damage after light exposure. This research aims to clarify the immune cell roles in AMD, aiming to inform therapies for prevention of vision loss in AMD patients.

This proposal leverages recent discoveries of microglia heterogeneity in the retina to investigate how distinct subtypes contribute differently to AMD pathogenesis. Rather than treating immune cells as a single population, this study dissects functional diversity within immune subsets to identify therapeutic targets. The use of genetically targeted models offers a precise way to dissect these mechanisms in vivo.

This study will provide mechanistic insight into how specific microglia subsets contribute to AMD, a leading cause of irreversible vision loss. The results may uncover novel therapeutic targets that could target microglial subtypes to suppress disease progression at any stage, offering a new strategy beyond current approaches. By highlighting the functional diversity of microglial responses in the retina, this research may open new avenues for immune-based interventions to preserve vision.