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Q. Huang, C. M. Sorenson, N. Sheibani; PEDF Deficient Mice Exhibit an Enhanced Rate of Retinal Vascular Expansion and Are More Sensitive to Hyperoxia-Mediated Vessel Obliteration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):523.
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Pigment epithelium derived factor (PEDF) is an endogenous inhibitor of angiogenesis. However, its physiological role during vascular development and neovascularization remains elusive. This report investigates the role of PEDF in normal postnatal vascularization of retina and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR) using PEDF-deficient (PEDF-/-) mice.
Retinal vascular density was assessed in wild type and PEDF-/- mice during postnatal retinal vascularization by determining the density and ratios of endothelial cells (EC) and pericytes (PC) in retinal trypsin digests. Retinal vascular cells were identified by cell-specific staining of wholemount retina preparations and eye frozen sections. The rates of proliferation and apoptosis of vascular cells were determined by BrdU and TUNEL staining, respectively. Retinal neovascularization during OIR was assessed by collagen IV staining of retina wholemounts and determining the number of vascular cell nuclei on vitreous side of retinal serial sections.
The retinal trypsin digests indicated that the ratio of EC to PC was significantly higher in PEDF-/- mice compared to wild type mice at postnatal day 21 (P21). This was mainly attributed to increased number of EC in the absence of PEDF. There was no significant difference in the number of PC. We observed increased rate of proliferation in retinal vasculature of PEDF-/- mice, which was somewhat compensated for by an increase in the rate of apoptosis. Staining of the retinal wholemounts and eye frozen sections indicated postnatal retinal vascularization expansion occurred at a faster rate in the absence of PEDF, and was more prominent at earlier time points, when PEDF expression is normally high (prior to P21). PEDF-/- mice exhibited enhanced sensitivity to hyperoxia-mediated vessel obliteration during OIR compared to wild type mice. However, there was no significant difference in the degree of retinal neovascularization.
We demonstrate that PEDF is an important modulator of postnatal retinal vascularization and in its absence retinal vascularization proceeds at a faster rate and is more susceptible to hyperoxia-mediated vessel obliteration.
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