The Open Biology Journal

2009, 2 : 141-148
Published online 2009 November 25. DOI: 10.2174/1874196700902010141
Publisher ID: TOBIOJ-2-141

RESEARCH ARTICLE
 Peroxisome Proliferator-Activated Receptor Expression in Murine Models and Humans with Age-related Macular Degeneration

Alexandra A. Herzlich , Xiaoyan Ding , Defen Shen , Robert J. Ross , Jingsheng Tuo and Chi-Chao Chan, *

* Address correspondence to this author at the 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD 20892-1857 USA; Tel: (301) 496-0417; Fax: (301) 402-8664; E-mail: chanc@nei.nih.gov

ABSTRACT

Peroxisome proliferator-activated receptors (PPARs) play a role in oxidative stress and VEGF regulation, which are closely related to age-related macular degeneration (AMD). PPAR γ expression and its downstream molecules were examined in fat-1 mice (transgenic mice that convert n-6 to n-3 fatty acids), Ccl2-/-/Cx3cr1-/- mice (an AMD model), ARPE19 cells (a human retinal pigment epithelial cell line, RPE, a cell type with a critical role in AMD), and human eyes with and without AMD. PPAR α, β, and γ, VEGF and receptors were determined by immunohistochemistry in the mice models, humans, and ARPE19 cells. Transcripts of PPARs, VEGF, MMP-9 and HO-1 were determined by RQ-PCR. PPARs were constitutively expressed in normal neuroretina and RPE of humans and mice. PPAR γ expression was increased in fat-1 and Ccl2-/-/Cx3cr1-/- mice. VEGF was decreased in fat-1 mice but increased in Ccl2-/-/Cx3cr1-/- mice. VEGF receptors were stable. VEGF, MMP9 and HO-1 transcript levels were increased in ARPE19 cells under H2O2 - induced oxidative stress. Human AMD retinas exhibited higher PPAR γ. The findings of increased expression of PPAR γ and its downstream proteins (VEGF, MMP9, and HO-1) in H2O2-treated ARPE19 cells, Ccl2-/-/Cx3cr1-/- mice, and human AMD eyes, but decreased VEGF in fat-1 mice, suggest that PPAR γ may play a role in AMD.