Retinal pigment epithelium lipid metabolic demands and therapeutic restoration

Abstract

One of the defining features of the retina is the tight metabolic coupling between cells such as photoreceptors and the retinal pigment epithelium (RPE). This necessitates the compartmentalization and proper substrate availability required for specialized processes such as photo-transduction. Glucose metabolism is preferential in many human cell types for adenosine triphosphate generation, yet fatty acid β-oxidation generates essential fuel for RPE. Here, we provide a brief overview of metabolic demands in both the healthy and dystrophic RPE with an emphasis on fatty acid oxidation. We outline therapies aimed at renormalizing this metabolism and explore future avenues for therapeutic intervention.

Keywords: Beta-oxidation; fatty acids; gene therapy; metabolic coupling; metabolism; mitochondria; retina; retinal pigment epithelium.

Figure 1

Overview of fatty acid metabolism in the retinal pigment epithelium. Light-damaged shed outer segment disks are phagocytized in the retinal pigment epithelium and broken down to fatty acids. Retinal pigment epithelium mitochondria use fatty acids in a process known as β-oxidation to generate adenosine triphosphate and ketone bodies which are shuttled back to photoreceptors to further glycolytic intermediates and subsequent energy production therein (created on Biorender.com)