Effects of calcitonin gene-related peptide in the eye. A study in rabbits and cats.

Calcitonin gene-related peptide (CGRP) has recently been demonstrated in sensory neurons of the eye. The purpose of the present study was to determine the effects of exogenous CGRP in the rabbit and cat eye. CGRP was injected intracamerally and the intraocular pressure was measured in cannulated eyes. The pupil diameter and the aqueous humor protein concentration were also measured. Indomethacin was used to prevent prostaglandin synthesis and tetrodotoxin (TTX) to block nerve conductance. In the rabbit eye, CGRP caused iridial hyperemia, a breakdown of the blood-aqueous barrier and increased intraocular pressure. These responses were dose-related. The increase in IOP as well as the breakdown of the blood-aqueous barrier could not be blocked with TTX or indomethacin. In cats CGRP caused a decrease in IOP and had only slight effect on the aqueous humor protein concentration. Neither in rabbits nor in cats had CGRP any detectable effect on the pupil size. Intracameral injection of 0.1 microgram (7.4 x 10(-11) moles) substance P together with 0.1 microgram (2.6 x 10(-11) moles) CGRP in rabbits caused maximal miosis but did not potentiate the intraocular effects of CGRP only. These results indicate that CGRP has marked vascular effects in the rabbit eye, causing a breakdown of the blood-aqueous barrier and increased IOP. The mechanism of this phenomenon does not involve prostaglandins neither nerve conduction, implying most likely a direct effect on the vascular smooth muscle. The mechanism of the decrease of IOP in cats remains unknown.