Purpose : CGRP (Calcitonin Gene-Related Peptide) and PACAP (Pituitary Adenylate Cyclase-Activating Peptide) are peptides with strong vasoactive effects. Retinal vasculature is known to be important in retinal ischemia, where vasodilating peptides could be a potential treatment. In addition, both peptides are known to be involved in migraine, a disease with vascular symptoms such as photosensitivity and aura, although they are hypothesized to also involve changes in the CNS. We therefore set out to investigate the potential effect of CGRP on the porcine retinal vasculature, and if the retinal and its vasculature could have sensory innervation.

Methods : We studied the porcine retinal vasculature and the ophthalmic artery using a wire myograph. Concentration dependence curves to CGRP and PACAP was obtained. We furthermore performed retrograde tracer experiments, where the dye DiI was injected intravitreal in male Sprague Dawley rats, where we traced the marker back to the trigeminal ganglion.

Results : CGRP was shown to be a strong vasodilator ( Emax dilation 83 ± 5 %) of the ophthalmic artery, whereas PACAP was very weakly vasodilating ( Emax dilation 37 ± 22 %). In contrast, the retinal vasculature was slightly more sensitive to PACAP (Emax dilation 40 ± 12 %) than CGRP (Emax dilation 29 ± 9 %). Our retrograde tracing experiment showed that there are indeed sensory neurons that innervate, the retina, and our next step is confirming the peptide identity of these neurons.

Conclusions : The ophthalmic artery, dilated strongly in response to CGRP. More interestingly, the porcine retinal vasculature relaxed in response to both PACAP and CGRP. We show that nerves originating from the trigeminal ganglion innervate the rat retina, and could therefore be the source of the sensory and vasoactive peptides. Nevertheless, innervation of the retinal vasculature is controversial, and there are other experimental data showing that CGRP is present locally in the retina, which could also be the peptide source. We conclude that CGRP and PACAP has vasoactive effects in the retinal vasculature, which could contribute to understanding migraine symptoms and in addition, be a potential treatment for ischemic eye disease.