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R.A. Renard, J. Cao, Y. Liu, H. Song, K.D. Anderson, G.D. Yancopoulos, S.J. Wiegand; Genetic Deletion of Pigment Epithelium–Derived Factor (PEDF) Does Not Alter the Development, or Subsequent Regression, of Pathological Neovascularization in a Mouse Model of Oxygen–Induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3258.
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Purpose: We have reported previously that genetic deletion of PEDF does not disrupt the normal development of vascular compartmentalization within the eye, (e.g. corneal, lens and vitreous remain completely avascular), and that the angioarchitecture and microvessel density of the retina are also normal in PEDF null mice (IOVS, 2003, 44:2888, Abstr.). While these findings demonstrate that endogenous PEDF does not play any appreciable role in normal ocular vascular development, it remained possible that PEDF might act as an endogenous inhibitor of pathological angiogenesis. To test this hypothesis, we have employed the murine model of oxygen–induced retinopathy (OIR) to determine whether the development or resolution of retinal neovascularization might be altered by genetic deletion of PEDF. Methods: Mice heterozygous for PEDF deletion were bred to generate litters comprising PEDF null, PEDF (+/–) and wild–type (PEDF +/+) offspring. Dams and their litters were placed in a hyperoxic environment (75% O2) on post–natal day 7 (PN7) and returned to room air on PN12. Eyes were collected on PN19, serial sections were cut and stained with H&E, and the extent neovascularization was assessed by counting nuclei outside the inner limiting membrane. The retina of the remaining eye was flat–mounted and stained with fluoresceinated Lectin (G. Simplicifolia, B4) and photographed. Retinas were then ranked by severity of pathological neovascularization. Both nuclear counts and the ranking of retinal flat–mounts were done by two independent observers who were masked to the genotype of the specimens. In another study, litters exposed to hyperoxia were euthanized on PN 29, to determine whether spontaneous regression of the retinal neovascularization was delayed in PEDF null animals. Results: PEDF null mice exposed to a hyperoxic environment from PN7–12 did not develop more extensive retinal neovascularization than their wild–type littermates, as determined either by rank analysis of flat mounts or nuclear counts in cross–sections. Moreover, the subsequent resolution of the neovascularization did not appear to be less complete in PEDF null mice on PN29, as determined by evaluation of retinal flat–mounts. Further analysis is in progress. Conclusions: These results do not support the hypothesis that PEDF functions as an important modulator of angiogenesis during normal development, or as an endogenous inhibitor of pathological angiogenesis.
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