Abstract
Age-related macular degeneration (AMD) is one of the most common degenerative eye diseases among the older population. One of the primary pathological features of AMD is the accumulation of fatty deposits known as drusen between the retinal pigment epithelium (RPE) and Bruch’s membrane in the eye. Few options exist that can slow AMD-associated retinal degeneration. One may be to enhance the RPE’s ability to oxidize fatty acids to delay or prevent drusen accumulation. Firsocostat is a small molecule that increases fatty acid oxidation in the liver. We determined the ability of Firsocostat to increase fatty acid oxidation and to decrease lipid contents in human induced pluripotent stem cells (iPSC) differentiated into RPE. In iPSC-RPE, firsocostat boosts fatty acid oxidation, remodels lipid profiles, and reduces apolipoprotein release. These data suggest that firsocostat may alleviate a pathological increase in drusen deposits and can help to preserve vision in AMD patients.
Funding: Funding: D.T.H is supported by a Brightfocus Foundation Postdoctoral Fellowship (M2022003F). J.B.H is supported by NEI RO1EY06641, RO1EY017863 and R21032597 and Foundation Fighting Blindness TA-NMT-0522-0826-UWA-TRAP.