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

Abstract

Thrombospondin-1 (TSP-1) is a glycoprotein involved in activation of latent transforming growth factor β (TGFβ) 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.