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Vadim Fedulov, Frank W Blixt, Karin D Sörensen, Lars Edvinsson, Karin Warfvinge, Kristian Agmund Haanes; Effects of Calcitonin Gene-related Peptide on the rat ciliary artery vasodilation and retinal function. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2645. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Calcitonin Gene-related Peptide (CGRP) has gained recent interest in several fields related to vascular research. While there is a growing recognition that CGRP signalling is involved in the symptoms of migraine, the effects of CGRP in the eye have not been well established. In addition, it has also been hypothesized that CGRP could be applied as a treatment retinal disease where upregulation of vasoconstrictive peptides has been well documented. We therefore set out to determine the effects of exogenous CGRP on the vasculature and the function of rat eye.
Concentration response curves to CGRP on the ophthalmic arteries from male Sprague Dawley rats were studied using a wire myograph. The effect of subconjunctival CGRP (10μl of 100 μM) on the ciliary arteries was investigated in vivo using fundus imaging. To investigate the vasoactive effect of CGRP on retina function, electroretinogram (ERG) was performed. Immunohistochemistry was applied to visualize the innervation of the ciliary and ophthalmic artery.
CGRP caused a strong vasodilation in the ophthalmic artery (Emax dilation 68 ± 6 %). Furthermore, CGRP caused a rapid and large vasodilation of the ciliary arteries following subconjunctival application. The functional consequence of ciliary artery vasodilation resulting from CGRP application under the conjunctiva of the eyeball was investigated in dark-adapted rats. Interestingly, the ERG data showed an average of 22 ± 9 % increase in B wave and 25 ± 5 % increase in A wave amplitudes compared to the control eye. Immunohistochemistry confirmed that CGRP fibres are found along both the ophthalmic and ciliary artery.
Based on our data, we can confirm that the ciliary and ophthalmic artery is innervated by CGRP containing fibres. Subconjunctival addition of CGRP to the rat eye resulted in dilation of ciliary artery and increased amplitudes of both the A-wave and the B-wave measured with ERG. These findings have a potential for increasing the understanding of functional consequences of modulating the vasculature of the eye. On one hand, increases in A-wave and B-wave amplitude could explain the increased photosensitivity observed in migraine patients. On the other hand, several ischemic eye disorders result from vasoconstriction of vasculature in the eye, and application of exogenous CGRP in these patients could be used as a treatment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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