Uveitis is the leading cause of legal blindness in the United States. Elucidation of initial events in the development of uveitis could provide new therapeutic approaches to the management of this blinding disease. These studies are based on the hypothesis that bone marrow-derived cells initiate uveitis by presenting retinal antigens to CD4+T-cells and such bone marrow-derived APCs may be present in the retina and/or choroid. This hypothesis will be tested using bone marrow chimeras with adoptive transfer of S-antigen specific T-cell lines. Specifically, the application will: (1) determine the role of bone marrow-derived cells in experimental autoimmune uveoretinitis (EAU) by transfer of specific T-cells to chimeras, (2) identify and localize the bone marrow-derived cells in retina and choroid and (3) determine the cytokine profile of these cells during the development of uveitis. This will be accomplished by a team of investigators with expertise in immunopathology, immunohistochemistry, in situ molecular techniques and molecular biology.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010727-03
Application #
2459154
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1995-08-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Doheny Eye Institute
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Gullapalli, V K; Zhang, J; Pararajasegaram, G et al. (2000) Hematopoietically derived retinal perivascular microglia initiate uveoretinitis in experimental autoimmune uveitis. Graefes Arch Clin Exp Ophthalmol 238:319-25
Matsubara, T; Pararajasegaram, G; Wu, G S et al. (1999) Retinal microglia differentially express phenotypic markers of antigen-presenting cells in vitro. Invest Ophthalmol Vis Sci 40:3186-93
Ishimoto, S; Zhang, J; Gullapalli, V K et al. (1998) Antigen-presenting cells in experimental autoimmune uveoretinitis. Exp Eye Res 67:539-48
Zhang, J; Wu, G S; Ishimoto, S et al. (1997) Expression of major histocompatibility complex molecules in rodent retina. Immunohistochemical study. Invest Ophthalmol Vis Sci 38:1848-57