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  • 标题:Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration
  • 作者:Norimitsu Ban ; Tae Jun Lee ; Abdoulaye Sene
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2018
  • 卷号:59
  • 期号:8
  • 页码:1414-1423
  • DOI:10.1194/jlr.M084442
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要: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.
  • 关键词:ATP binding cassette transporter G1 ; cholesterol/dietary ; cholesterol/efflux ; eye/retina ; neurons ; aging
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