Abstracto

Expression of the CGRP family of peptides and their receptors in the rat retina

Karin Warfvinge, Lars Edvinsson

The calcitonin gene-related peptide (CGRP) family of peptides includes CGRP itself, calcitonin, adrenomedullin and amylin. They are all related to each other vis-à-vis peptide sequence and receptor biology. Understanding expression of the peptides and their receptors lays the foundation for more deeply understanding their physiology and pathophysiology in eye diseases, and their plausible therapeutic possibility. We have designed an in-depth study of the expression of the CGRP family of peptides and their receptors in rat retina using single and double immunohistochemistry with antibodies against: CGRP, calcitonin, adrenomedullin, amylin, CLR, RAMP1, RAMP2, RAMP3 and CTR. We observed that CGRP was mainly seen in Müller cell end feet, adrenomedullin and calcitonin were expressed in the blood vessels, while amylin was widely distributed within the retina. CGRP receptors consist of CLR/RAMP1. These two receptor components are co-localized in the nerve fiber layer, RAMP2/3 are found in the nuclear layers, and CTR in the plexiform layers. The only co-localization ligand/ligand, receptor/receptor or ligand/receptor was CLR/RAMP1, and thereby suggesting a functional receptor. CTR is the only component that is needed for the calcitonin receptor. We conclude that in the normal rat retina, functional CGRP receptors and also calcitonin receptors (consisting of only CTR) exist, but not adrenomedullin or amylin receptors.