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J. M. Barnett, G. W. McCollum, J. S. Penn; Inhibition of Retinal Vascular Growth and Development in PPARβ-/- Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2954.
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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of transcription factors activated by a number of ligands including fatty acids, NSAIDs, fibrates and prostaglandins. Prostacyclin (PGI2), a prostaglandin naturally produced in endothelial cells, has been shown to be an endogenous ligand for PPARβ. We have found that antagonism of PPARβ inhibits endothelial cell proliferation and tube formation. In the present studies, we sought to determine influence of PPARβ in promoting retinal vascular growth and development using PPARβ-/- animals.
Seven days following birth (P7), the eyes of PPARβ-/- mice were fixed in 4% paraformaldehyde, the retinas were dissected and then washed with PBS. The retinas were then treated overnight at 4°C with 0.5% Triton X-100 and 1% BSA in PBS, washed twice with PBS and incubated with 20µg/ml FITC-conjugated Griffonia simplicifolia isolectin B4 at 4°C overnight. The retinas were then washed with PBS, flat-mounted using Dako mounting medium and viewed by confocal microscopy at a magnification of 4X.
Comparison of vascular development in PPARβ-/- vs. wild type mouse retinas showed a 59.8% increase in avascular area of the mutant strain, specifically 4.47±0.45 mm2 compared to 2.79±0.39 mm2 (p<0.0001). The vasculature of the PPARβ-/- retinas also demonstrated significantly fewer vessels and larger periarterial capillary free zones, demonstrated by vascular densities 39.7±4.6% for PPARβ-/- mice vs. 49.0±5.6% for wild type mice; p=0.0111.
The deletion of PPARβ in the mutant animals resulted in a retarded retinal vascular growth by P7. The mutant mice also displayed a decreased retinal vascular density. Given these phenotypic features, the deletion of PPARβ is likely to result in a significant effect on neovascularization in retinopathy models. Thus PPARβ should be further investigated as a possible therapeutic target for retinal vascular pathologies.
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