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Publication : Thrombospondin-1-deficient mice exhibit increased vascular density during retinal vascular development and are less sensitive to hyperoxia-mediated vessel obliteration.

First Author  Wang S Year  2003
Journal  Dev Dyn Volume  228
Issue  4 Pages  630-42
PubMed ID  14648840 Mgi Jnum  J:128776
Mgi Id  MGI:3768008 Doi  10.1002/dvdy.10412
Citation  Wang S, et al. (2003) Thrombospondin-1-deficient mice exhibit increased vascular density during retinal vascular development and are less sensitive to hyperoxia-mediated vessel obliteration. Dev Dyn 228(4):630-42
abstractText  Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. Its expression is most prominent during the late stages of vascular development and in the adult vasculature. Our previous studies have shown that TSP1 expression promotes a quiescent, differentiated phenotype of vascular endothelial cells. However, the physiological role TSP1 plays during vascular development and neovascularization requires further delineation. Here, we investigated the role of TSP1 during development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy. The retinal vascular density was increased in TSP1-deficient (TSP1-/-) mice compared with wild-type mice. This finding was mainly attributed to increased number of retinal endothelial cells in TSP1-/- mice. During oxygen-induced ischemic retinopathy, the developing retinal vasculature of TSP1-/- mice was less sensitive to vessel obliteration induced by hyperoxia but exhibited a similar level of neovascularization induced by normoxia compared with wild-type mice. This finding is consistent with the similar pattern of VEGF expression detected in wild-type and TSP1-/- mice. Furthermore, the increased expression of TSP1 during development of retinal vasculature was not affected by oxygen-induced ischemic retinopathy. In addition, the regression of ocular embryonic (hyaloid) vessels, as well as the newly formed retinal vessels during oxygen-induced ischemic retinopathy, was delayed in TSP1-/- mice. Therefore, TSP1 is a modulator of vascular homeostasis and its expression is essential for appropriate remodeling and maturation of retinal vasculature.
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