Universität zu Köln

Storti, Federica, Raphael, Gabriele, Griesser, Vera, Klee, Katrin, Drawnel, Faye, Willburger, Carolin, Scholz, Rebecca, Langmann, Thomas, von Eckardstein, Arnold, Fingerle, Juergen, Grimm, Christian ORCID: 0000-0001-9318-4352 and Maugeais, Cyrille (2017). Regulated efflux of photoreceptor outer segment-derived cholesterol by human RPE cells. Exp. Eye Res., 165. S. 65 - 78. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-0007

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Abstract

Genetic studies have linked age-related macular degeneration (AMD) to genes involved in high-density lipoprotein (HDL) metabolism, including ATP-binding cassette transporter Al (ABCA1). The retinal pigment epithelium (RPE) handles large amounts of lipids, among others cholesterol, partially derived from internalized photoreceptor outer segments (OS) and lipids physiologically accumulate in the aging eye. To analyze the potential function of ABCA1 in the eye, we measured cholesterol efflux, the first step of HDL generation, in RPE cells. We show the expression of selected genes related to HDL metabolism in mouse and human eyecups as well as in ARPE-19 and human primary RPE cells. Immunofluorescence staining revealed localization of ABCA1 on both sides of polarized RPE cells. This was functionally confirmed by directional efflux to apolipoprotein Al (ApoA-I) of H-3-labeled cholesterol given to the cells via serum or via OS. ABCA1 expression and activity was modulated using a liver-X-receptor (LXR) agonist and an ABCA1 neutralizing antibody, demonstrating that the efflux was ABCA1-dependent. We concluded that the ABCAl-mediated lipid efflux pathway, and hence HDL biosynthesis, is functional in RPE cells towards both the basal (choroidal) and apical (subretinal) space. Impaired activity of the pathway might cause age-related perturbations of lipid homeostasis in the outer retina and thus may contribute to disease development and/or progression. (C) 2017 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Storti, Federica UNSPECIFIED UNSPECIFIED UNSPECIFIED Raphael, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Griesser, Vera UNSPECIFIED UNSPECIFIED UNSPECIFIED Klee, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Drawnel, Faye UNSPECIFIED UNSPECIFIED UNSPECIFIED Willburger, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED von Eckardstein, Arnold UNSPECIFIED UNSPECIFIED UNSPECIFIED Fingerle, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimm, Christian UNSPECIFIED orcid.org/0000-0001-9318-4352 UNSPECIFIED Maugeais, Cyrille UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-210118
DOI:	10.1016/j.exer.2017.09.008
Journal or Publication Title:	Exp. Eye Res.
Volume:	165
Page Range:	S. 65 - 78
Date:	2017
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication:	LONDON
ISSN:	1096-0007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUBRETINAL DRUSENOID DEPOSITS; APOLIPOPROTEIN-A-I; DENSITY-LIPOPROTEIN; MACULAR DEGENERATION; GENETIC-VARIANTS; LIPID-METABOLISM; HUMAN RETINA; AGE; ABCA1; EXPRESSION Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21011