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Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.

ABSTRACT: Photoreceptors have high intrinsic metabolic demand and are exquisitely sensitive to metabolic perturbation. In addition, they shed a large portion of their outer segment lipid membranes in a circadian manner, increasing the metabolic burden on the outer retina associated with the resynthesis of cell membranes and disposal of the cellular cargo. Here, we demonstrate that deletion of both ABCA1 and ABCG1 in rod photoreceptors leads to age-related accumulation of cholesterol metabolites in the outer retina, photoreceptor dysfunction, degeneration of rod outer segments, and ultimately blindness. A high-fat diet significantly accelerates rod neurodegeneration and vision loss, further highlighting the role of lipid homeostasis in regulating photoreceptor neurodegeneration and vision.

SUBMITTER: Ban N

PROVIDER: S-EPMC6071770 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.

Ban Norimitsu N Lee Tae Jun TJ Sene Abdoulaye A Dong Zhenyu Z Santeford Andrea A Lin Jonathan B JB Ory Daniel S DS Apte Rajendra S RS

Journal of lipid research 20180626 8

Photoreceptors have high intrinsic metabolic demand and are exquisitely sensitive to metabolic perturbation. In addition, they shed a large portion of their outer segment lipid membranes in a circadian manner, increasing the metabolic burden on the outer retina associated with the resynthesis of cell membranes and disposal of the cellular cargo. Here, we demonstrate that deletion of both ABCA1 and ABCG1 in rod photoreceptors leads to age-related accumulation of cholesterol metabolites in the out ...[more]

PMID: 29946056

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