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G Gao, Y Li, J Fant, CE Crosson, SP Becerra, JX Ma; Rat Strain Difference in Ischemic Regulation of VEGF and PEDF and in Susceptibilities to Retinal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2754.
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Purpose: Sprague Dawley (SD) rats are more resistant to ischemia-induced retinal neovascularization (IRN) compared to Brown Norway (BN) rats. The purpose of this study is to understand the molecular basis responsible for the rat strain difference. Methods: IRN was produced by exposure of newborn BN or SD rats to 75% oxygen for 7 days followed by room air. Retinal neovascularization was evaluated by means of angiography and vascular cell counts in the neural retina cross-sections. Changes in mRNA and protein levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) were measured in the retina by Northern and Western blot analyses at selected time following return of rats to roomair. Results: Exposure to constant hyperoxia followed by normoxia induced significant retinal neovascularization in BN rats, but not in SD rats. These results confirmed a strain difference in susceptibility to IRN in rat retina. BN rats exposed to hyperoxia showed a 50% reduction in retinal PEDF, and a 5-fold increase of VEGF at the protein level, resulting in an increased VEGF/PEDF ratio. The similar changes were also observed at mRNA level in BN rats with IRN. However, SD rats exposed to hyperoxia showed less and shorter changes in PEDF and VEGF levels than that in BN rats. In age-matched normal BN and SD rats, there was no detectable difference in the basal VEGF/PEDF ratio between the strains. Conclusions: These studies provide initial evidence that different regulations of angiogenic inhibitors and stimulators under ischemia are responsible for the differences in susceptibility to IRN in SD and BN rats. The pigmented BN rat is more suitable for the ischemia-induced retinopathy model.
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