Advertisement

PPAR Nuclear Receptors and Altered RPE Lipid Metabolism in Age-Related Macular Degeneration

  • Goldis Malek
  • Peng Hu
  • Albert Wielgus
  • Mary Dwyer
  • Scott Cousins
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 664)

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.

Keywords

Retinal Pigment Epithelial Peroxisome Proliferator Activate Receptor Retinal Pigment Epithelial Cell ARPE19 Cell Human Retinal Pigment Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by a grant from the International Retinal Research Foundation and Research to Prevent Blindness.

References

  1. Anderson DH, Mullins RF et al (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 134(3):411–431CrossRefPubMedGoogle Scholar
  2. Anderson DH, Talaga KC et al (2004) Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res 78(2):243–256CrossRefPubMedGoogle Scholar
  3. Arteel GE (2008) New role of plasminogen activator inhibitor-1 in alcohol-induced liver injury. J Gastroenterol Hepatol 23(Suppl 1):S54–S59CrossRefPubMedGoogle Scholar
  4. Bird AC, Bressler NM et al (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 39(5):367–374CrossRefPubMedGoogle Scholar
  5. Canter JA, Olson LM et al (2008) Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration. PLoS ONE 3(5):e2091CrossRefPubMedGoogle Scholar
  6. Chawla A, Boisvert WA et al (2001) A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell 7(1):161–171CrossRefPubMedGoogle Scholar
  7. Chinetti G, Fruchart JC et al (2001) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall. Z Kardiol 90(Suppl 3):125–132PubMedGoogle Scholar
  8. Crabb JW, Miyagi M et al (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A 99(23):14682–14687CrossRefPubMedGoogle Scholar
  9. Curcio CA, Millican CL (1999) Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol 117(3):329–339PubMedGoogle Scholar
  10. Curcio CA, Presley JB et al (2005) Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp Eye Res 81(6):731–741CrossRefPubMedGoogle Scholar
  11. Edwards AO, Ritter R 3rd et al (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308(5720):421–424CrossRefPubMedGoogle Scholar
  12. Fiotti N, Pedio M et al (2005) MMP-9 microsatellite polymorphism and susceptibility to exudative form of age-related macular degeneration. Genet Med 7(4):272–277CrossRefPubMedGoogle Scholar
  13. Green WR (1999) Histopathology of age-related macular degeneration. Mol Vis 5:27PubMedGoogle Scholar
  14. Hageman GS, Anderson DH et al (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A 102(20):7227–7232CrossRefPubMedGoogle Scholar
  15. Hageman GS, Luthert PJ et al (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 20(6):705–732CrossRefPubMedGoogle Scholar
  16. Hageman GS, Mullins RF et al (1999) Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells. FASEB J 13(3):477–484PubMedGoogle Scholar
  17. Haines JL, Hauser MA et al (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308(5720):419–421CrossRefPubMedGoogle Scholar
  18. Johnson LV, Leitner WP et al (2002) The Alzheimer’s A beta-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci U S A 99(18):11830–11835CrossRefPubMedGoogle Scholar
  19. Kersten S, Desvergne B et al (2000) Roles of PPARs in health and disease. Nature 405(6785):421–424CrossRefPubMedGoogle Scholar
  20. Klein R, Klein BE et al (2007) Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 114(2):253–262CrossRefPubMedGoogle Scholar
  21. Klein RJ, Zeiss C et al (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308(5720):385–389CrossRefPubMedGoogle Scholar
  22. Malek G, Li CM et al (2003) Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am J Pathol 162(2):413–425PubMedGoogle Scholar
  23. Moore KJ, Fitzgerald ML et al (2001) Peroxisome proliferator-activated receptors in macrophage biology: friend or foe? Curr Opin Lipidol 12(5):519–527CrossRefPubMedGoogle Scholar
  24. Murata T, He S et al (2000) Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neovascularization. Invest Ophthalmol Vis Sci 41(8):2309–2317PubMedGoogle Scholar
  25. Nunn AV, Bell J et al (2007) The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance. Nucl Recept 5(1):1CrossRefPubMedGoogle Scholar
  26. Olefsky JM, Saltiel AR (2000) PPAR gamma and the treatment of insulin resistance. Trends Endocrinol Metab 11(9):362–368CrossRefPubMedGoogle Scholar
  27. Ross RJ, Bojanowski CM et al (2007) The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci 48(3):1128–1132CrossRefPubMedGoogle Scholar
  28. Sampath H, Ntambi JM (2005) Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 25:317–340CrossRefPubMedGoogle Scholar
  29. SanGiovanni JP, Chew EY et al (2007) The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20. Arch Ophthalmol 125(5):671–679Google Scholar
  30. SanGiovanni JP, Chew EY et al (2008) The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS Report No. 23. Arch Ophthalmol 126(9):1274–1279Google Scholar
  31. Schmidt S, Klaver C et al (2002) A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy. Ophthalmic Genet 23(4):209–223CrossRefPubMedGoogle Scholar
  32. Sime PJ (2008) The antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis. J Investig Med 56(2):534–538PubMedGoogle Scholar
  33. Yang Z, Camp NJ et al (2006) A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science 314(5801):992–993CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Goldis Malek
    • 1
  • Peng Hu
    • 1
  • Albert Wielgus
    • 1
  • Mary Dwyer
    • 1
  • Scott Cousins
    • 1
    • 2
  1. 1.Department of OphthalmologyDuke UniversityDurhamUSA
  2. 2.The Duke Center for Macular Diseases and Albert Eye Research Institute, Duke University Eye CenterDurhamUSA

Personalised recommendations