Activation of the TRPV1 channel attenuates N-methyl-D-aspartic acid-induced neuronal injury in the rat retina.

Abstract

Capsaicin, a transient receptor potential vanilloid type1 (TRPV1) agonist, has been reported to protect against ischemia-reperfusion injury in various organs, including the brain, heart, and kidney, whereas activation of TRPV1 was also reported to contribute to neurodegeneration, including pressure-induced retinal ganglion cell death in vitro. We histologically investigated the effects of capsaicin and SA13353, TRPV1 agonists, on retinal injury induced by intravitreal N-methyl-d-aspartic acid (NMDA; 200 nmol/eye) in rats in vivo. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal NMDA injection. Capsaicin (5.0 nmol/eye) was intravitreally admianeously with NMDA injection. SA13353 (10mg/kg) was intraperitoneally administered 15 min before NMDA injection. Morphometric evaluation at 7 days after NMDA injection showed that intravitreal NMDA injection resulted in ganglion cell loss. Capsaicin and SA13353 almost completely prevented this damage. Treatment with capsazepine (TRPV1 antagonist, 0.5 nmol/eye), CGRP (8-37) (calcitonin gene-related peptide (CGRP) receptor antagonist, 0.5 pmol/eye), or RP67580 (tachykinin NK1 receptor antagonist, 0.5 nmol/eye) almost completely negated the protective effect of capsaicin in the NMDA-injected rats. Seven days after intravitreal NMDA injection, the cell number of retinal ganglion cell was significantly smaller than in the eye that had received capsaicin in B6.Cg-TgN(Thy1-CFP)23Jrs/J transgenic mice that express the enhanced cyan fluorescent protein in retinal ganglion cells in the retina. These results suggested that activation of TRPV1 protects retinal neurons from the injury induced by intravitreal NMDA in rats in vivo. Activation of CGRP and tachykinin NK1 receptors is possibly involved in underlying protective mechanisms.

• Authors: Kenji Sakamoto, Taiyo Kuroki, Yui Okuno, Haruna Sekiya, Akihiro Watanabe, Tomonori Sagawa, Hiroko Ito, Aya Mizuta, Asami Mori, Tsutomu Nakahara, Kunio Ishii
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 733 Pg. 13-22 (Jun 15 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24704373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• 1-(2-(1-adamantyl)ethyl)-1-pentyl-3-(3-(4-pyridyl)propyl)urea
• Pyridines
• TRPV Cation Channels
• Trpv1 protein, rat
• enhanced cyan fluorescent protein
• Green Fluorescent Proteins
• N-Methylaspartate
• Urea
• Capsaicin

Topics

• Animals
• Capsaicin (pharmacology)
• Cell Survival (drug effects)
• Green Fluorescent Proteins (genetics)
• Injections, Intraperitoneal
• Intravitreal Injections
• Male
• Mice
• Mice, Transgenic
• N-Methylaspartate (toxicity)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Retinal Ganglion Cells (drug effects, metabolism, pathology)
• TRPV Cation Channels (agonists)
• Urea (analogs & derivatives, pharmacology)