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N Sheibani, S Wang, Z-F Wu, X Su, CM Sorenson; Thrombospondin-1 Deficient Mice Exhibit Increased Retinal Vascular Density During Development and Oxygen-Induced Ischemic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4023.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Negative regulators of angiogenesis play a major role in maintaining vascular homeostasis. Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis and it is present in vitreous and aqueous humor. This report investigates the role of TSP1 in retinal vascular development and hypoxia-induced neovascularization. Methods: Retinal vascular density was assessed in wild type and TSP1-/- mice during development by determining the number of endothelial cells and pericytes in retinal trypsin digests and endothelial cells in retinal serial sections. Retinal neovascularization in oxygen-induced ischemic retinopathy was assessed by type IV collagen staining of the retinal whole mounts. Results: The retinal trypsin digests indicated that the ratio of endothelial cells to pericytes was similar in three weeks old TSP1-/- mice compared to wild type. This was consistent with the number of endothelial cells in retinal serial sections. However, the ratio of endothelial cells to pericytes decreased by half by six weeks of age in the wild type mice, while the ratio remained the same in TSP1-/- mice. Therefore, the retinal vascular density of TSP1-/- mice was twice that of the wild type mice. This is mainly attributed to the higher number of endothelial cells in TSP1-/- mice. In the oxygen-induced ischemic retinopathy model, TSP1-/- mice exhibited delayed blood vessel regression during the hyperoxia phase, followed with a more robust neovascular response during the hypoxic phase. Conclusions: We demonstrate that TSP1 is an important modulator of retinal vascular homeostasis and its absence contributes to aberrant vascular development and excessive neovascularization.
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