Abstract
Abstract: :
Purpose:To determine if intravitreal administration of recombinant PEDF could prevent the morphological changes in the retina noted after sympathectomy Methods:Sixty–day old female Sprague–Dawley rats were sympathectomized by surgical removal of the superior cervical ganglion. Three weeks after sympathectomy, rats received 1 intravitreal injection of either saline or 2 microliters containing 2 micrograms recombinant PEDF into both the contralateral and sympathectomized eye. Three weeks after the PEDF injection, rat retinas were harvested for real–time polymerase chain reaction for PEDF mRNA, western blotting for PEDF protein, and immunohistochemistry for morphology studies. Results:Retina from sympathectomized eyes receiving saline treatment had significantly reduced PEDF mRNA and protein expression relative to the contralateral eye receiving saline treatment. These results are similar to previous work and indicate that injection alone did not alter the results. Intravitreal PEDF administration to sympathectomized eyes returned both mRNA and protein levels to those of the contralateral eye. PEDF administration also normalized retinal morphometry to prevent the sympathectomy–induced increases in capillary density of the outer plexiform layers, as well as the ganglion cell layer. Conclusions:These results suggest that one injection of PEDF can restore protein and mRNA levels to those noted in an untreated animal. Furthermore, these results also indicate that one injection of PEDF can reverse the morphological changes noted after sympathectomy in the retina. Intravitreal injection of PEDF may be able to maintain its effect on the retinal vasculature for longer times than previously investigated. In this study, the results indicate that PEDF effects were noted 3 weeks after a single injection of a low–dose recombinant PEDF. These findings have significant clinical relevance for drug discovery efforts toward angiostatic therapies.
Keywords: growth factors/growth factor receptors • innervation: neural regulation • diabetic retinopathy