The ocular surface is constantly subjected to antigenic challenge from the external environment. These antigens, which incude viruses, bacteria, and toxic substances, threaten corneal integrity and may lead to severe visual impairment or blindness. To defend against this antigenic threat, the eye may rely primarily upon the secretory immune system. The long-range objective of this grant application is to improve our understanding of how hormones regulate the secretory immune system in the eye. Proposed studies on the rat model include determination of the characteristics and mechanisms of hormone action on the oculrr secretory immune system. Experimental procedures involve radioimmunoassays, chromatographic techniques, cell cultures, immunocytochemistry, autoradiography, hormone and SC receptor binding studies, Scatchard plot analyses, and endocrine organ ablation and hormone reconstitution studies.
Specific aims are: (1) To further characterize the hormonal regulation of the ocular secretory immune system. These studies include: (a) evaluation of the acute and chronic effects of androgen treatment on secretory component (SC), IgA, and IgG levels in tears and exorbital gland tissue; (b) determination of whether the androgen control of the secretory immune system is unique to the eye; and (c) assessment of the role of the hypothalamic-pituitary axis in the androgen regulation of SC, IgA, and IgG levels in tears. (2) To examine the mechanisms by which hormones regulate the ocular secretory immune system. These experiments involve: (a) determination of the number, affinity, and cellular location of androgen receptors in ocular tissues; (b) examination of the androgen control of exorbital gland acinar cell synthesis and expression of SC after hormone treatment in vivo or in vitro; and (c) determination of how androgens regulate IgA in the eye. Results from these experiments should advance our knowledge of the endocrine regulation of ocular mucosal immunity. In addition, findings may have health relatedness for the eye, because (a) they examine the control of the ocular secretory immune system, which may prevent bacterial colonization and viral invasion of the surface of the eye; and (b) they address the ocular mechanisms and consequences of androgen treatment, which has been used to treat immunological disorders of the lacrimal gland.
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