@article{f34b647600d340c6bbed101fae2f5053,
title = "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.—Ban, N., T. J. Lee, A. Sene, Z. Dong, A. Santeford, J. B. Lin, D. S. Ory, and R. S. Apte. Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.",
keywords = "ATP binding cassette transporter G1, Aging, Cholesterol/dietary, Cholesterol/efflux, Eye/retina, Neurons",
author = "Norimitsu Ban and Lee, {Tae Jun} and Abdoulaye Sene and Zhenyu Dong and Andrea Santeford and Lin, {Jonathan B.} and Ory, {Daniel S.} and Apte, {Rajendra S.}",
note = "Funding Information: This work was supported by National Institutes of Health Grants R01 EY019287 (R.S.A.) and P30 EY02687 (Vision Core Grant), the International Retinal Research Foundation (N.B.), the Starr Foundation (R.S.A.); the Carl Marshall and Mildred Almen Reeves Foundation (R.S.A.); the Bill and Emily Kuzma Family Gift for Retinal Research (R.S.A.), Research to Prevent Blindness Physician-Scientist and Nelson Trust Awards (R.S.A.), the Jeffrey Fort Innovation Fund (R.S.A.); the Glenn Foundation for Medical Research, and the Thome Memorial Foundation (R.S.A.). Additional support was provided by an unrestricted Research to Prevent Blindness Grant to the Department of Ophthalmology and Visual Sciences of Washington University School of Medicine. J.B.L. was supported by the Washington University in St. Louis Medical Scientist Training Program (National Institutes of Health Grant T32 GM07200), the Washington University in St. Louis Institute of Clinical and Translational Sciences (National Institutes of Health Grants UL1 TR002345 and TL1 TR002344), and the VitreoRetinal Surgery Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflict of interest. Manuscript received 16 February 2018 and in revised form 12 June 2018. Published, JLR Papers in Press, June 26, 2018 DOI https://doi.org/10.1194/jlr.M084442 Funding Information: This work was supported by National Institutes of Health Grants R01 EY019287 (R.S.A.) and P30 EY02687 (Vision Core Grant), the International Retinal Research Foundation (N.B.), the Starr Foundation (R.S.A.); the Carl Marshall and Mildred Almen Reeves Foundation (R.S.A.); the Bill and Emily Kuzma Family Gift for Retinal Research (R.S.A.), Research to Prevent Blindness Physician-Scientist and Nelson Trust Awards (R.S.A.), the Jeffrey Fort Innovation Fund (R.S.A.); the Glenn Foundation for Medical Research, and the Thome Memorial Foundation (R.S.A.). Additional support was provided by an unrestricted Research to Prevent Blindness Grant to the Department of Ophthalmology and Visual Sciences of Washington University School of Medicine. J.B.L. was supported by the Washington University in St. Louis Medical Scientist Training Program (National Institutes of Health Grant T32 GM07200), the Washington University in St. Louis Institute of Clinical and Translational Sciences (National Institutes of Health Grants UL1 TR002345 and TL1 TR002344), and the VitreoRetinal Surgery Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflict of interest. Publisher Copyright: Copyright {\textcopyright} 2018 Ban et al.",
year = "2018",
doi = "10.1194/jlr.M084442",
language = "English",
volume = "59",
pages = "1414--1423",
journal = "Journal of Lipid Research",
issn = "0022-2275",
number = "8",
}