The white blood cells which are involved in uveal tract immune-mediated inflammation must adhere to and traverse endothelium to reach the perivascular tissues, where they cause disease. Local factors which modulate lymphocyte responses in eye, including inhibitors of lymphocyte proliferation have been demonstrated in vitreous and in perivascular glial cells. Inhibitors of endothelial cell growth have been demonstrated in vitreous, which are believed to be partly responsible for the normal avascularity of vitreous, one of these appears to be TGF beta. Much work suggests endothelial cells can stimulate lymphocyte proliferation and process antigen. This project aims at analyzing relationships between endothelial cells, lymphocyte function, and the inhibitors previously isolated. It includes a) purification of the lymphocyte inhibitors, and determining if it is the same as the endothelial inhibitor, b) determining at which state of the processes of lymphocyte entry into the tissue, differentiation, and proliferation of lymphocytes the inhibitors works, c) determining whether it is a direct effect on lymphocytes or is mediated through cells which stimulate lymphocytes such as monocytes or endothelial cells, d) determining whether the factor is effective in vivo as well as in tissue culture, e) determining which subpopulations of lymphocytes the factor affects, f) determining whether purified inhibitors of endothelial cell growth have similar effects. The long-term objective is to use these to plan treatments which can suppress the local immune response occurring in immune-mediated ocular disease.
| Eisenstein, R; Grant-Bertacchini, D (1991) Growth inhibitory activities in avascular tissues are recognized by anti-transforming growth factor beta antibodies. Curr Eye Res 10:157-62 |
