Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Authors

William Dan, 1 Ga Hyun Park, 1 Shruti Vemaraju, 2 , 3 Amy D. Wu, 1 Kristina Perez, 4 Meenakshi Rao, 4 Dan E. Berkowitz, 5 Richard A. Lang, 2 , 3 , 6 , 7 and Peter D. Yim 1 , *

Affiliations

"1Department of Anesthesiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States
2The Visual Systems Group, Abrahamson Pediatric Eye Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
3Division of Pediatric Ophthalmology, Center for Chronobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
4Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
5Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama, Birmingham, AL, United States
6Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
7Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
Edited by: Sal A. Baker, University of Nevada, Reno, United States
Reviewed by: Masahiro Kono, Medical University of South Carolina, United States; Takahiro Yamashita, Kyoto University, Japan; Thomas W. Gould, University of Nevada School of Medicine, United States
*Correspondence: Peter D. Yim, [email protected]
This article was submitted to Gastrointestinal Sciences, a section of the journal Frontiers in Physiology"

Topic

Cell Biology, Optogenetics

Abstract

"Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon. Precontracted murine colon segments demonstrated blue light (BL) -mediated relaxation ex vivo. This photorelaxation was wavelength specific and was increased with the administration of the chromophore 9-cis retinal and a G protein receptor kinase 2 (GRK2) inhibitor. Light-mediated relaxation of the colon was not inhibited by L-NAME or tetrodotoxin (TTX). Furthermore, BL exposure in the presence of 9-cis retinal decreased the frequency of colonic migrating motor complexes (CMMC) in spontaneously contracting mouse colons ex vivo. These results demonstrate for the first time a receptor-mediated photorelaxation of colonic smooth muscle and implicate opsins as possible new targets in the treatment of spasmodic gastrointestinal dysmotility.

Keywords: colon, motility, opsin, relaxation, neuron

DOI: https://dx.doi.org/ 10.3389/fphys.2021.744294

Extract

Following the establishment of stable contractions, colon rings were exposed to blue (435 nm λ) or red (635 nm λ) light at 5 mW intensity from 5 cm distance (PE4000, CoolLED, Andover, England), or no light.

Product Associated Features

The pE-4000 Universal Illumination System offers 16 selectable wavelengths from 365 - 770 nm, making it a highly flexible illuminator covering a wide variety of fluorophores

Product Type

pE-4000

Journal

Front. Physiol.

Year of Publication

2019

Country of Publication

Switzerland