PPAR nuclear receptors and altered RPE lipid metabolism in age-related macular degeneration

Adv Exp Med Biol. 2010:664:429-36. doi: 10.1007/978-1-4419-1399-9_49.

Abstract

The pathophysiology of 'early' dry age-related macular degeneration (ARMD), characterized by the accumulation of lipid and protein-rich sub-retinal deposits remains largely unknown. Accumulation and dysregulated turnover of lipids as well as extracellular matrix (ECM) molecules in sub-retinal pigment epithelial (RPE) deposits and Bruch's membrane, itself an ECM, play a role in ARMD. Epidemiological studies have shown an increased risk for the disease associated with higher dietary intake of long chain poly-unsaturated fatty acids (LCPUFA) and specifically more so for n-6 versus n-3 fatty acids. PUFAs are membrane targets of lipid peroxidation and natural ligands for the nuclear receptors, peroxisome proliferator activated receptors (PPAR). Here we investigated the expression of genes involved in lipid metabolism and expression of the three isoforms of PPARs in an immortalized cell line of human RPE cells (ARPE19) in the presence or absence of fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Fatty Acids, Unsaturated / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Macular Degeneration / genetics*
  • Peroxisome Proliferator-Activated Receptors / genetics*
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / pathology
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Fatty Acids, Unsaturated
  • Peroxisome Proliferator-Activated Receptors
  • Protein Isoforms
  • RNA, Messenger