Neural Control of Ocular Immune Privilege

A bstract : Ocular immune privilege arises from interactions between the immune apparatus and the eye itself, thereby providing immune protection for the eye that is devoid of sight‐threatening inflammation. On the one hand, antigens injected intraocularly elicit deviant systemic immune responses that are devoid of immunogenic inflammation (Anterior Chamber‐Associated Immune Deviation, ACAID). On the other hand, the ocular microenvironment (aqueous humor, secreted by cells that surround this chamber) suppresses intraocular expression of immunogenic inflammation. Several lines of evidence indicate that ocular immune privilege is under neural control. First, aqueous humor contains neuropeptides (α‐MSH, VIP, CGRP) that inhibit and alter the functional properties of T lymphocytes and macrophages. Second, when corneal nerves are severed, the tissues surrounding the anterior chamber cease secreting immunosuppressive factors and ACAID fails‐until the nerves regrow. Third, light deprivation abolishes the capacity of the anterior chamber to support ACAID induction, a process that is sensitive to neuropeptides and melatonin. The photoreceptor(s) responsible for ACAID are connected to the nervous system and may reside in the anterior segment and/or the retina. Thus, neural elements from the central nervous system and within the eye help to shape both the induction and the expression of ocular immunity, thereby promoting immune privilege.