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Novel Role for CGRP in Aqueous Humor Outflow
Timur A Mavlyutov1, Samer E Bilal1, Tania Sharmin1
1Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison Wisconsin, United States.
Investigative Ophthalmology & Visual Science
|July 16, 2026
Summary
Calcitonin gene related peptide (CGRP) influences trabecular meshwork (TM) function by enhancing phagocytosis and blocking fibrosis. CGRP-positive nerves are concentrated in high-flow regions, suggesting a role in regulating aqueous humor outflow.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Calcitonin gene related peptide (CGRP)-positive nerve fibers are abundant in the trabecular meshwork (TM) and Schlemm's canal (SC).
- These neurons release CGRP, a neuropeptide with known physiological effects.
Purpose of the Study:
- To investigate the role of CGRP in maintaining TM homeostasis.
- To explore the relationship between CGRP-positive innervation and segmental aqueous humor outflow regions.
Main Methods:
- Western blot analysis confirmed CGRP receptor expression in human TM and SC cells.
- In vitro studies assessed CGRP's effect on phagocytosis and TGFβ2-induced expression of α-SMA and COL1A1.
- In vivo studies in mice quantified CGRP neurite density and CGRP receptor (CALCRL) expression in relation to segmental flow regions.
Main Results:
- CGRP treatment enhanced phagocytosis and inhibited TGFβ2-induced collagen and α-SMA expression in TM cells.
- CGRP receptors were detected in human TM and SC cells.
- A higher density of CGRP-positive nerve fibers and CGRP receptor expression was observed in high-flow regions of the mouse anterior segment.
Conclusions:
- CGRP plays a significant role in modulating TM homeostatic functions, including phagocytosis and extracellular matrix production.
- The distribution of CGRP innervation suggests its involvement in the regulation of segmental aqueous humor outflow pathways.
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