The present Research Plan will examine immune regulation within the eye and addresses two topics: (1) analysis of immune rejection of syngeneic intraocular tumors and (2) analysis of immunological privilege in the anterior chamber. Gaining a clear understanding of immune regulation within the eye is paramount importance from several perspectives. Clinical observations suggest that intraocular neoplasms can undergo immunological rejection. Although a robust intraocular immune response may be effective in ridding the eye of a life-threatening neoplasm, it may inflict irreparable damage to normal ocular tissues. In other cases, intraocular tumor rejection is precisely focused and does not damage delicate ocular structures. The first portion of this Research Plan will thoroughly examine these two basic patterns for intraocular tumor rejection. The investigations will characterize the immunoregulatory mechanisms that determine which immunological pathway tumor rejection will follow. Further experiments will seek ways to manipulate these immunological mechanisms to the benefit of the host. The second portion of this Research Plan will examine the immunologic privilege that is extended to allografts placed into the anterior chamber. The proposed investigations seek to identify the mechanisms responsible for inducing and sustaining immune privilege in the anterior chamber. Understanding this process may lead to methods for suppressing autoimmune disorders or unwanted responses to therapeutic organ grafts. The long term goal for this project is to thoroughly understand immune regulation as it pertains to intraocular tumors and tissue grafts. This, in turn, may suggest methods for focusing a protective immune response against intraocular neoplasms or pathogens without inflicting injury to normal ocular tissues. Understanding immune privilege may lead to strategies for promoting long term survival of therapeutic organ grafts.
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