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RA Saunders, G Gao, J Fant, P Kaufman, S Kruger, J Ma; Regulation of PEDF and VEGF by Inducing Photoreceptor Apoptosis: A Possible Mechanism for Laser Photocoagulation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1287.
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Purpose: Retinal photocoagulation induces regression of retinal neovascularization and decreases the incidence of severe vision loss in retinopathy of prematurity, but the molecular mechanisms of action are unknown. We studied the effect of laser treatment on the expression of endogenous angiogenic factors using a rat model. Methods: Oxygen-induced retinopathy (OIR) was produced by exposure of newborn Brown Norway rats to 75% oxygen followed by room air. Normal adult Brown Norway rats and OIR rats were subjected to retinal photocoagulation using a diode laser (50-200 mW energy @ 0.2 seconds duration) and approximately 200 burns per retina. Apoptosis of retinal photoceceptors induced by laser treatment were examined by TUNEL and DNA fragmentation. Retinal angiography was performed using high molecular weight fluorescein and examined using a fluorescent microscope. Protein levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the retina were measured by Western blot analysis. Results: Laser treatment at an early stage of OIR (post natal day 13) decreased the avascular area by approximately 60% in our OIR model compared with the control eyes without laser, suggesting a therapeutic effect. Treatment at a later stage (post natal day 16) of OIR decreased the avascular area by 35%. There was apoptosis of retinal photoreceptor cells with a commensurate decrease in the angiogenic stimulator VEGF to approximate 40% of the control level and elevation of the angiogenic inhibitor PEDF level by 2.5-fold. Conclusion: The up-regulation of PEDF and down-regulation of VEGF by laser photocoagulation may lead to restoration of the normal balance of these cytokines and represent a mechanism for the regression of OIR after laser photocoagulation. The effects of laser treatment on the regulation of VEGF and PEDF are mediated at least in part by photoreceptor cell apoptosis.
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