DISTRIBUTION AND EFFECTS OF PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE IN THE RABBIT EYE

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreac tivity was demonstrated by immunocytochemistry together with calcitoni n gene-related peptide (CGRP)-like immunoreactivity in small to medium -sized neurons in the trigeminal ganglion and in nerve fibres in the i ris, ciliary body, cornea, choroid and sclera of the rabbit eye. The r egional distribution of PACAP-27- and PACAP-38-like immunoreactivity i n the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pa ttern resembled that of CGRP-like immunoreactivity, which is a well-kn own constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the a nterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin p retreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aque ous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde on to the cornea, or intravi treal injection of endotoxin or bovine serum albumin. Also the concent ration of CGRP-like immunoreactivity in the aqueous humor was increase d greatly. Both in vivo and in vitro studies showed that capsaicin cau sed a parallel release of PACAP-like immunoreactivity and CGRP-like im munoreactivity from the uvea. injection of PACAP-27 and PACAP-38 resul ted in the release of CGRP-like immunoreactivity (and PACAP-like immun oreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were als o found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.