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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007732-03
Application #
3264759
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1990-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Sinai Samaritan Medical Center Milwaukee
Department
Type
DUNS #
City
Milwaukee
State
WI
Country
United States
Zip Code
53201