Onchocerciasis is the third major cause of 'preventable' blindness in the world. If affects some 50 million people causing 1 million cases of 'legal' blindness and several million more cases of severe visual impairment. It contributes to deprivation, hunger, and elevated birthrate and has a depressing impact on the economies of developing nations. The mechanisms which lead to ocular disease are poorly understood: The pathology and immunology of this disease will be studied in detail in mice using Onchocerca cervicalis microfilariae (mf).
The specific aims are: 1) To characterize the cellular and humoral responses in ocular onchocerciasis and to relate these to the development of anterior and posterior segment disease. 2) To determine the effects of vitamin A deprivation on ocular onchocerciasis, and, 3) To investigate the effects of chemotherapy in conjunction with the immune status and level of vitamin A deprivation of the host. Several inbred strains of mice will be used varying in their genetic susceptibility/resistance of mf. O. cervicalis mf, harvested from infected horse skins will be used to sensitize mice intraocularly or s.c. and to challenge via various intraocular routes. Infections will be monitored by slit lamp biomicroscopy, fluorescein angiography, EM, light microscopy and immunocytochemical techniques. Vitamin A deprivation will be monitored by ERG. Initially DEC and ivermectin will be used in the chemotherapy studies. The investigation will attempt to determine a) the possible roles of eosinophils, neutrophils, B and T (subset0 lymphocytes, macrophages, mast cells, immune complexes and autoantibodies in anterior and posterior segment disease; b) the effect of prior systemic and intraocular sensitization with live mf, mf fractions and excretory and secretory products; and c) the effect of passive transfer of antibody and/or cells. Vitamin A deficiency coexists with onchocerciasis in many areas and has been suggested as contributing to ocular onchocercal disease. Hypovitaminosis A both enhances susceptibility to numerous infectious agents through physiological and immunological changes and is enhanced by immune status and drugs can induce, or potentiate or depress the immune response. A laboratory mouse model could advance considerably our understanding of ocular onchocerciasis, its relationship to host immunity and provide a tool for evaluation of potential vaccines and chemotherapeutic agents.
| Callahan, H L; Crouch, R K; James, E R (1990) Hydrogen peroxide is the most toxic oxygen species for Onchocerca cervicalis microfilariae. Parasitology 100 Pt 3:407-15 |
| Lackey, A; James, E R; Sakanari, J A et al. (1989) Extracellular proteases of Onchocerca. Exp Parasitol 68:176-85 |
| Callahan, H L; Wakeman, J M; Crouch, R K et al. (1989) An in vitro radiolabel uptake viability assay for Onchocerca microfilariae. J Parasitol 75:142-4 |
| Moran, C T; James, E R (1987) Equine ocular pathology ascribed to Onchocerca cervicalis infection: a re-examination. Trop Med Parasitol 38:287-8 |
| James, E R; Smith, B; Donnelly, J (1986) Invasion of the mouse eye by Onchocerca microfilariae. Trop Med Parasitol 37:359-60 |
