Abstract
The purpose of this study was to determine whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)γ ligand, altered growth factor expression in the choroid-RPE complex of Koletsky rats. Using lean and obese Koletsky rats fed a normal or rosiglitazone-supplemented diet, gene and protein expression of vascular endothelial growth factor (VEGF), pigment epithelial derived growth factor (PEDF), angiopoietin 1, and its receptor, Tie-2, were assessed. Both gene expression and protein expression of PEDF were significantly increased in both obese and lean Koletsky rats treated with rosiglitazone diet. Gene expression of VEGF, angiopoietin-1 and Tie-2 were increased after rosiglitazone treatment, without changes in protein expression. Since PPARγ ligands have been implicated in vascular remodeling, these results suggest that upregulation of PEDF expression may be a potential mechanism in the rat choroid-RPE complex.
Highlights
It is clear that that neovascularization of the choroid can lead to the vision loss associated with macular degeneration
It is clear that the obese Koletsky rats have hyperlipidemia and hyperinsulinemia when compared to their lean littermates (Table 1)
The addition of rosiglitazone to the diet elicited a number of alterations to both the lean and the obese Koletsky rat, including an increase in total body weight in obese animals
Summary
It is clear that that neovascularization of the choroid can lead to the vision loss associated with macular degeneration. In addition to regulating PEDF and VEGF, other agents are under investigation to regulate the choroidal vasculature, including peroxisome proliferator-activated receptor (PPAR)γ ligands One such ligand, rosiglitazone has been of particular interest in diabetes, as it has been shown to alter insulin sensitivities, a common problem in type 2 diabetes [5]. In order to better understand potential mechanisms by which rosiglitazone could alter the choroidal vasculature, these preliminary experiments investigated a number of choroid growth factors known to be involved in vascular changes. For these studies, we used lean and obese Koletsky rats treated with rosiglitazone (a PPAR γ ligand). Key growth factors investigated include vascular endothelial growth factor (VEGF), angiopoietin (Ang1) and its receptor (Tie2) and pigment epithelial derived factor (PEDF)
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