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C.K. Chan, L.N. Pham, J. Zhou, C. Spee, S.J. Ryan, D.R. Hinton; Early Regulation of Strain-Dependent Retinal Angiogenesis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1500.
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Purpose: The the etiology of angiogenic retinopathies is multi-factorial and the extent of their severity is largely unpredictable. Recent experiments indicate that genetic determinants may contribute to corneal angiogenic susceptibility to exogenous basic fibroblast growth factor and vascular endothelial growth factor (VEGF). We investigated the strain-dependence of murine retinal neovascularization and early regulation of angiogenic gene expression in response to hypoxia. Methods: To induce retinal neovascularization, neonatal mice (p7) of two inbred mouse strains were exposed to 75% oxygen for 5 days and room air (relative hypoxia) for an additional 5 days. On postnatal day 17, the pups were euthanized; and their eyes were enucleated and frozen for cryosectioning. Total neovascular surface area was assessed by endothelial specific isolectin B4 immunohistochemistry on every fifth serial section (10 µm) from a reference point of nasal cornea to optic nerve (12 sections per eye). Total RNA was isolated from posterior poles of each animal subjected to the hyperoxia-hypoxia model to investigate early regulation of strain-dependent retinal angiogenesis. Hypoxic regulation of VEGF and angiopoietin-2 (Ang-2) gene expression were evaluated using real-time PCR. Results: Intra-vitreal neovascularization in 129s3/SvIMJ (N=10) pups was over twice that of c57BL/6J (N=12) (p<0.0001). Intra-retinal neovascularization was also significantly increased in 129s3/SVIMJ compared to c57BL/6J (p<0.001). Real-time PCR results revealed no significant differences in VEGF or Ang-2 gene expression within the first 24 hours of hypoxia. Conclusions: This data indicates that genetic factors may also be involved in determining the severity of retinal angiogenesis. However, early differential regulation of VEGF and Ang-2 may not contribute to strain-dependent retinal angiogenesis. Furthermore, elucidation and modulation of specific genetic factors may provide suitable targets for pharmacologic therapy of angiogenesis-dependent diseases such as diabetic retinopathy and retinopathy of prematurity.
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