Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

5-12-2017

Publication Source

Journal of Biological Chemistry

Volume

292

Issue

19

Start Page

8038

Last Page

8047

DOI

10.1074/jbc.M116.770784

Abstract

Daily, the retinal pigment epithelium (RPE) ingests a bolus of lipid and protein in the form of phagocytized photoreceptor outer segments (OS). The RPE, like the liver, expresses enzymes required for fatty acid oxidation and ketogenesis. This suggests that these pathways play a role in the disposal of lipids from ingested OS, as well as providing a mechanism for recycling metabolic intermediates back to the outer retina. In this study, we examined whether OS phagocytosis was linked to ketogenesis. We found increased levels of β-hydroxybutyrate (β-HB) in the apical medium following ingestion of OS by human fetal RPE and ARPE19 cells cultured on Transwell inserts. No increase in ketogenesis was observed following ingestion of oxidized OS or latex beads. Our studies further defined the connection between OS phagocytosis and ketogenesis in wild-type mice and mice with defects in phagosome maturation using a mouse RPE explant model. In explant studies, the levels of β-HB released were temporally correlated with OS phagocytic burst after light onset. In the Mreg−/− mouse where phagosome maturation is delayed, there was a temporal shift in the release of β-HB. An even more pronounced shift in maximal β-HB production was observed in the Abca4−/− RPE, in which loss of the ATP-binding cassette A4 transporter results in defective phagosome processing and accumulation of lipid debris. These studies suggest that FAO and ketogenesis are key to supporting the metabolism of the RPE and preventing the accumulation of lipids that lead to oxidative stress and mitochondrial dysfunction.

Copyright/Permission Statement

This research was originally published in the Journal of Biological Chemistry. Reyes-Reveles, J., Dhingra, A., Alexander, D., Bragin, A., Philp, N. J., & Boesze-Battaglia, K. (2017). Phagocytosis-dependent ketogenesis in retinal pigment epithelium. The Journal of Biological Chemistry, 292(19), 8038–8047. http://doi.org/10.1074/jbc.M116.770784© the American Society for Biochemistry and Molecular Biology .

Keywords

fatty acid, lipid metabolism, phagocytosis, photoreceptor, photosynthesis, retinal metabolism

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Date Posted: 01 March 2022

This document has been peer reviewed.