THE EFFECT OF LIGHT ON THE OCULAR IMMUNE RESPONSE

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DESCRIPTION (Adapted from applicant's abstract): The anterior chamber of the eye is a unique microenvironment in which immunological processes, especially inflammatory responses, are either impaired or totally inhibited. The profound suppression of delayed-type hypersensitivity (DTH) to antigens introduced into the anterior chamber has been termed anterior chamber-associated immune deviation (ACAID) and is believed to be the primary mechanism for sustaining immune privilege within the eye. The present application will examine a curious phenomenon in which mice reared or adapted to the dark cannot develop ACAID and instead, develop positive DTH responses to antigens introduced into the anterior chamber. The working hypothesis is that light deprivation stimulates the intraocular production of interleukin-1 (IL-1) and/or substance P (SP) which in turn activates T cells in the anterior chamber. The net result is activation, rather than down- regulation, of antigen-specific immunity. Four specific aims will be addressed pursuant to this hypothesis. They are: (1) determine the mechanisms by which anti-IL-1 alpha antibody reverses the dark-rearing effect; (2) explore the role of neuropeptides in both the induction and abolition of ACAID; (3) explore the function of inflammatory cells that accumulate following anterior chamber inoculation of antigen in dark- and light-adapted mice; and (4) explore the effect of light and dark exposure on the resident ocular cells and immune effector mechanisms in the eye. The long range goal of this project is to better understand the molecular basis of ACAID and immune privilege.