Peptidergic innervation of the retinal vasculature and optic nerve head

Using immunocytochemistry, the authors studied the peptidergic innervation to the vasculature of the optic nerve and retina in the rhesus monkey and rat. In the monkey, beaded nerve fibers immunoreactive to the vasoactive peptides, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal peptide (VIP), are present in the adventitia and perivascular space along the course of the central retinal artery within the optic nerve. The CGRP and SP immunoreactivities fully co-localize. Perivascular peptidergic nerve fibers terminate as the blood vessel enters the globe and do not follow the branches of the central retinal artery inside the eye. Within the substance of the optic nerve behind the lamina cribrosa, small blood vessels occasionally are supplied with CGRP-, SP-, and sometimes NPY- or VIP-immunoreactive nerve fibers. Of special note, fine nerve fibers not clearly related to blood vessels are seen within the lamina cribrosa; their simultaneous immunoreactivity to CGRP and SP suggests a sensory function. In the rat as in the monkey, the retinal arterioles beyond the surface of the optic disc lack evident peptidergic innervation. Perhaps an explanation for the known physiologic reactivity of the retinal circulation to neurohumors in the absence of recognizable peripheral innervation can be based on comparison to the brain where intraparenchymal blood vessels may be regulated by local neurons. Since the inner plexiform layer has abundant amacrine-derived nerve processes containing classical neurotransmitters and/or neuropeptides, a local mechanism coupled to intrinsic retinal activity might contribute to the regulation of the circulation.