ABSTRACT
Retinopathy .................................................................................. 333 14.2.3 Attenuation of Retinal Vascular Development and
Neovascularization in Mice Overexpressing Tsp1 in the Lens .................................................................................... 334
14.3 Establishment of Mouse Retinal Endothelial Cells ................................... 334 14.3.1 Enhanced Proangiogenic Signaling in TSP1−/− Retinal
Endothelial Cells .......................................................................... 336 14.3.2 Decreased Proapoptotic Signaling in TSP1−/− Retinal
Endothelial Cells .......................................................................... 336 14.3.3 Downregulation of TSP1 Expression in Wild-Type Retinal
Endothelial Cells .......................................................................... 337 14.4 TSP1 and Modulation of Nitric Oxide Synthase Activity ......................... 339 14.5 Summary .................................................................................................... 341 References .............................................................................................................. 342
Thrombospondin-1 (TSP1) is a member of the TSP family of matricellular proteins, currently containing five members (TSP1-5) (1,2). The highly restricted spatial and temporal expression of TSPs indicates important roles for these molecules during
development (3). TSP1, or platelet TSP, was the first member of this family identified in platelets α-granules (4). TSP expression during eye development has been previously demonstrated throughout the optic vesicle, lens, retina, Bruch’s membrane, and nerve fiber layer. In the adult retina, very little expression is detectable in cell bodies and ganglion cells. It is now known that TSP1 is expressed by a variety of cells in culture, including endothelial cells, astrocytes, pericytes, retinal pigmented epithelial cells, fibroblasts, and smooth muscle cells. In fact, production of TSP1 and TSP2 by astrocytes was recently shown to drive synaptogenesis in retinal neurons (5). TSP1 interacts with at least a dozen cell surface receptors expressed in various combinations on different cell types. It is the interaction of TSP1 with these cellspecific receptors that elicits a cell-type-specific response.
