Effects of some neuropeptides on the uvea

Abstract

This lecture summarizes studies on the effects of some of the neuropeptides which seem to be present in somatosensory and autonomic nerves in the uvea. Release of these peptides is likely to explain nerve induced effects in the eye which are not due to classical transmitters. Trigeminal nerve fibres in the eye seem to contain substance P (SP), calcitonin gene-related peptide (CGRP), and cholecystokinin (CCK), parasympathetic nerve fibers from the facial nerve seem to contain vasoactive intestinal polypeptide (VIP), and peptide with histidine and isoleucine terminals (PHI), and sympathetic nerves seem to contain neuropeptide Y (NPY). Retrograde trigeminal nerve stimulation in rabbits causes hyperemia, miosis, a breakdown of the blood-aqueous barrier to plasma proteins and a rise in intraocular pressure (IOP). There is release of SP and CGRP or related peptides. The miosis seems to be due to SP and the other effects to CGRP and small amounts of arachidonic acid metabolites released by the peptides. SP has no miotic effect in monkeys and cats. However, CCK is a potent miotic in monkeys and causes contraction of the human pupillary sphincter muscle. It has no such effect in the lower species. The effect of CCK in primates seems to derive from the presence of CCK receptors of the A-type on the pupillary sphincter muscle, and can be blocked by lorglumide. Miosis can be produced in cats by the peptide endothelin; this effect is due to release of arachidonic acid metabolites. Facial nerve stimulation causes vasodilation in the uvea of rabbits, cats and monkeys. The effect cannot be abolished by muscarinic blocking agents. The non-muscarinic vasodilation in rabbits may be explained by release of VIP and PHI. These peptides have no vasodilatory effects on the uvea in cats suggesting that a third peptide may be involved in facial nerve-induced vasodilation in that species. VIP stimulates aqueous humor formation in monkeys. NPY is a vasoconstrictor in the rabbit eye. Release of this peptide, preferably at high stimulation frequencies, may explain non-adrenergic vasoconstriction caused by sympathetic nerve stimulation. In cats, sympathetic vasoconstriction in the uvea seems to be due mainly to adrenergic mechanisms. The results indicate that there are remarkable species variations in the effects of neuropeptides and that arachidonic acid metabolites mediate some of the effects of regulatory peptides in the eye.