Role of Lipids (Deposits) in Causing Dry AMD

Project Summary

The goal of the project is to understand the role of a novel lipid enzyme that makes specific types of omega-3 and omega-6 fatty acids and how this might play a role in macular degeneration. We have made a mouse deficient of this lipid enzyme and found that it accelerates aging in the eye and shows some changes resembling dry AMD. We hypothesize that this mouse could be a novel model to study the mechanism of development of dry AMD. In this grant, we propose to see how the complement system, a pathway implicated in AMD, interacts with this lipid enzyme pathway. We will inhibit complement activity in our mouse model and see how this affects the vision of the mouse. Next, we will look specifically at the role of this lipid enzyme in the retinal pigment epithelium (RPE), a key cell type involved in AMD. Using state-of-the-art gene-editing techniques, we will knock out the function of this lipid enzyme in RPE cells grown in culture and see whether that affects cell death, metabolic function, or aging in these cells. This study will provide a better understanding of how this lipid enzyme affects aging in the eye and how it contributes to the AMD disease process. We expect that work performed under this proposal will create a solid foundation for future studies to design novel therapeutics that target aging to help treat dry AMD.