Accumulation of thrombospondin-1 in post-operative capsular fibrosis and its down-regulation in lens cells during lens fiber formation.

Thrombospondin-1 (TSP-1) is a glycoprotein involved in activation of latent transforming growth factor beta (TGFbeta) expression. We examined changes in its expression pattern during human capsular opacification (PCO) and anterior subcapsular cataractogenesis (ASC), as well as in a healing injured mouse lens. Its expression pattern was also compared in a mouse embryonic lens with that in an adult lens. Based on immunohistochemistry under light microscopy, TSP-1 expression and other matrix components were evident in the anterior epithelium of an uninjured human lens, whereas fiber-differentiating cells in the equator of human lens lack TSP-1 immunoreactivity. In contrast, in post-operative human lens epithelial or fibroblastic cells, there was TSP-1 immunoreactivity, whereas it decreased in fiber-differentiating cells in PCO. Matrix components accumulated on the healing capsule also labeled with anti-TSP-1 antibody like antibodies against collagen I, IV, V and laminin. In uninjured, injured mouse lens epithelial cells and its matrix, there was TSP-1 expression. Embryonic lens cells in the posterior pole, undergoing differentiation to fiber cells, began to express TSP-1 protein at embryonic day (E) 11.5 whereas anterior epithelial cells started to express it at E13.5 in association with marked expression in central fiber cells. At E16.5, TSP-1 was detected in fibers just beneath the anterior epithelium, but the fiber mass showed minimal expression. At E18.5 and post-natally day 1, lens fiber TSP-1 expression was no longer seen. On the other hand, it was evident in both intact human anterior epithelial and dispersed mouse cells. The results indicate that there is TSP-1 expression in uninjured human and mouse lens epithelial cells and their fibrous tissue. In contrast, in post-operative lens cells differentiating to fiber cells, its expression levels decline. Further study is needed to clarify the roles of TSP-1 in modulating lens cell phenotype expression.