Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration

Norimitsu Ban, Tae Jun Lee, Abdoulaye Sene, Zhenyu Dong, Andrea Santeford, Jonathan B. Lin, Daniel S. Ory, Rajendra S. Apte

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1414-1423
Number of pages10
JournalJournal of lipid research
Volume59
Issue number8
DOIs
Publication statusPublished - 2018

Keywords

  • ATP binding cassette transporter G1
  • Aging
  • Cholesterol/dietary
  • Cholesterol/efflux
  • Eye/retina
  • Neurons

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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  • Cite this

    Ban, N., Lee, T. J., Sene, A., Dong, Z., Santeford, A., Lin, J. B., Ory, D. S., & Apte, R. S. (2018). Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration. Journal of lipid research, 59(8), 1414-1423. https://doi.org/10.1194/jlr.M084442