Uncovering the Hidden Link Between Liver Health and Macular Degeneration

This project aims to develop a human liver–eye microphysiological platform to define how aging-related hepatic metabolic dysfunction drives systemic complement activation and retinal pigment epithelium injury in age-related macular degeneration.

Age-related macular degeneration is the leading cause of blindness in the elderly, yet current treatments only slow progression and fail to address systemic drivers of disease. This project will develop a human liver–retina chip to uncover how age-related metabolic dysfunction in the liver triggers complement activation that damages retinal pigment epithelial cells. Understanding this cross-organ immune–metabolic axis will enable new therapeutic strategies to prevent vision loss and improve health outcomes in the aging population.

This proposal is innovative because it establishes the first human liver–eye platform designed to model how aging-related hepatic metabolic dysfunction drives systemic complement activation and downstream RPE injury in AMD. Unlike conventional animal or cell culture models that focus primarily on local ocular pathology, our system integrates human liver organoids and RPE tissues to directly investigate cross-organ immune–metabolic signaling. The platform also enables simultaneous testing of upstream metabolic interventions and downstream complement-targeted therapies, providing a novel framework for developing combination treatments for AMD.

Completion of this study will provide a platform to investigate how systemic metabolic aging and liver dysfunction contribute to AMD development and progression through complement-mediated injury. Our findings may identify new therapeutic targets that combine metabolic and complement-based interventions, ultimately supporting the development of more effective treatments for dry AMD, a condition that currently lacks curative therapies. More broadly, this work could improve public health by advancing strategies to preserve vision and quality of life in the rapidly growing aging population.