Peptidergic nerves in the eye, their source and potential pathophysiological relevance

Over the last five decades, several neuropeptides have been discovered which subsequently have been found to be highly conserved during evolution, to be widely distributed both in the central and peripheral nervous system and which act as neurotransmitters and/or neuromodulators. In the eye, the first peptide to be explored was substance P which was reported to be present in the retina but also in peripherally innervated tissues of the eye. Substance P is certainly the best characterized peptide which has been found in sensory neurons innervating the eye. Functionally, it has been shown to act trophically on corneal wound healing and to participate in the irritative response in lower mammals, a model for neurogenic inflammation, where it mediates the noncholinergic nonadrenergic contraction of the sphincter muscle. Over the last three decades, the interest has extended to investigate the presence and distribution of other neuropeptides including calcitonin gene-related peptide, vasoactive intestinal polypeptide, neuropeptide Y, pituitary adenylate cyclase-activating polypeptides, cholecystokinin, somatostatin, neuronal nitric oxide, galanin, neurokinin A or secretoneurin and important functional results have been obtained for these peptides. This review focuses on summarizing the current knowledge about neuropeptides in the eye excluding the retina and retinal pigment epithelium and to elucidate their potential functional significance.