PPAR nuclear receptors and altered RPE lipid metabolism in age-related macular degeneration.
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.
Malek
Goldis
G
Department of Ophthalmology, Duke University, Durham, NC, USA. gmalek@duke.edu
Hu
Peng
P
Wielgus
Albert
A
Dwyer
Mary
M
Cousins
Scott
S
D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger