NEUROPEPTIDES MODULATE IMMUNE DEVIATION INDUCED VIA THE ANTERIOR-CHAMBER OF THE EYE

Ag presentation via the anterior chamber of the eye results in a form of immune deviation termed anterior chamber-associated immune deviatio n (ACAID). The hallmarks of this response are the suppression of delay ed-type hypersensitivity with simultaneous induction of Ab production. In this study, we examined the role of the neuropeptides vasoactive i ntestinal peptide (VIP) and substance P (SP) and found that the levels of these two peptides are controlled by neurogenic stimulation of the eye by light, and that these molecules determine the outcome of Ag pr esentation in the eye. Mice reared under diurnal conditions had VIP in the iris and ciliary body (not free in aqueous humor) and low levels of SP. Mice that were reared in the dark (or dark-adapted) did not con tain detectable levels of VIP but had high levels of SP. The adaptatio n of diurnal mice to the dark eliminated VIP and increased SP, while a dapting dark-reared mice to the diurnal cycle increased VIP and reduce d SP. We then tested the hypothesis that immune reactions resulting fr om Ag presentation in the eye were linked to SP and VIP. We found that a VIP receptor antagonist, when injected into the eye with Ag, revers ed ACAID in diurnal mice, while a SP receptor antagonist restored ACAI D to dark-adapted mice. We further determined that injection of Ag or TNF-alpha induced VIP release, while SP was liberated into the aqueous humor following reexposure of dark-reared mice to light. Our results demonstrate a close linkage of intraocular immune reactions to neurope ptide levels in the eye.