Can Fatty Acid Oxidation Influence Drusen Levels in the Eye?

The overarching goal of this proposal is to determine whether altering lipid metabolism can decrease the burden of lipid-rich deposits (drusen).

Aim 1: We will culture patient-derived RPE cells that are genetically determined to accumulate lipid-rich deposits. We will determine whether treating these cells with inhibitors of acetyl-coA carboxylase (ACC) increases fatty acid oxidation rate, decreases lipid levels, and decreases the accumulation of lipid-rich deposits in culture. Aim 2: We will be using two distinct mouse models that each accumulate lipid-rich deposits. In these models, we will determine whether in vivo administration of two ACC inhibitors impacts circulating and tissue lipid metabolism as well as visual function.

The proposal is innovative because this treatment strategy has not previously been proposed or tested. It is also uniquely rigorous because we will integrate multiple experimental systems and multiple ACC inhibitors to make the interpretation of our data robust.

1. Benefit to the field – a new therapeutic modality that uses cellular metabolism to treat disease.
2. Benefit to the general public – a therapeutic avenue for AMD that is safe for humans and is immediately available for off-label use.