A substrain of the Sinclair miniature swine have cutaneous malignant melanomas that are cured by the animal's own immune system, but in the process the normal melanocytes of the uveal tract are destroyed creating a severe uveitis. The retina is damaged later causing diminution in electrical activity and function. The long-term objectives of the research on these animals is to determine the sequence of immunologic events that cause destruction of ocular tissue. Histologic studies will concentrate on the early invasion of the uveal tract by immune cells; identification of the cell types and the sequence in which they invade will be done by immunofluorescence using anti-T and anti-B lymphocyte antibody as well as anti-IgG and IgM antibody staining. Electron microscopy will be used to examine aspects of vasculitis, immune complex deposition, breaching of blood-retinal and blood-aqueous barriers, etc. Tissue cultures of swine uveal melanocytes have been established. These will be used as target cells for testing cytotoxic capacity of peripheral blood leukocytes serially isolated from animals undergoing ocular depigmentation. Immunologic work on the uveitis will include production of anti-B swine lymphocyte and anti-swine complement conjugates, tests for functional ability of B or T lymphocytes, detection of immune complexes by polyethylene glycol and Raji cell assays, and search for antibodies in aqueous humor or serum by Ouchterlony immunodiffusion or Western blot techniques. The ultimate objective is to gain a better idea of how Sinclair pigs can cure their own melanoma, and learn basic mechanisms that cause the uveitis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003680-06
Application #
3258098
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1981-05-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1988-11-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Richerson, J T; Burns, R P; Misfeldt, M L (1989) Association of uveal melanocyte destruction in melanoma-bearing swine with large granular lymphocyte cells. Invest Ophthalmol Vis Sci 30:2455-60
Richerson, J T; Misfeldt, M L (1989) Host environment as a modulating factor of swine natural killer cell activity. Vet Immunol Immunopathol 23:309-19
Feeney-Burns, L; Burns, R P; Gao, C L (1988) Ocular pathology in melanomatous Sinclair miniature swine. Am J Pathol 131:62-72
Burns, R P; Tidwell, M (1986) Experimental ocular malignant melanoma in Sinclair swine. Curr Eye Res 5:257-62
Feeney-Burns, L; Alspaugh, M; Burns, R P et al. (1985) Uveitis in melanomatous swine: lack of evidence for humoral immune melanocyte destruction. Invest Ophthalmol Vis Sci 26:551-60
Hightower, K R; Duncan, G; Harrison, S E (1985) Intracellular calcium concentration and calcium transport in the rabbit lens. Invest Ophthalmol Vis Sci 26:1032-4