Abstract
Abstract: :
Purpose:PEDF is one of the most potent anti–angiogentic factors in the eye. It is thought, that neovascularization in the eye depends on a delicate balance of angiogenic stimulators such as VEGF and anti–angiogenic factors, such as PEDF. Alterations in the VEGF/ PEDF ratio may be a main cause of pathological neovascularization, and the reason for the high sensitivity of some rat strains to hypoxic conditions. In this study the protein expression of VEGF and PEDF was measured in complete eyes of Wistar (W) and Long Evans (LE) rats, to find out more about their role during vascularization after birth and at older stages of postnatal development. . Methods:Immunocytochemical and Western blot analysis of PEDF and VEGF protein expression was assessed in complete eyes of LE and W rats from birth until 21 months of age. Results:Western results show, that the PEDF content in the eye was very similar in both rat strains, and that it was downregulated from birth on. There were no obvious differences between both rat strains regarding the location and signal intensity of PEDF in the retina. However, old W retinas that showed loss of photoreceptor cells and presence of large blood vessels in the choroid, seemed to stain stronger than intact LE retinas. Western results show that at birth, the VEGF content was comparable to PEDF and VEGF was steadily downregulated until 7 months, but increased at very high age, which lead to a strong increase in the VEGF/ PEDF ratio. There was no difference between both rat strains in the overall VEGF content and its location in the eye. VEGF staining intensities increased with age. Conclusions:The increasing content of VEGF together with the decreasing levels of PEDF in complete eyes of old developmental stages of both rat strains are consistent with studies that have reported a high VEGF/PEDF ratio in human eyes with age related macular degeneration (AMD), suggesting that a high VEGF/PEDF ratio might precede signs of AMD or might even be a prerequisite for pathological neovascularization in advanced age. Furthermore, our data indicate, that there are strain dependent differences in the susceptibility to a high VEGF/PEDF ratio, since only W retinas showed signs of degeneration, although VEGF/PEDF ratios were comparable in both rat strains.
Keywords: growth factors/growth factor receptors • neovascularization • retinal development