Activation of the TRPV1 channel attenuates N-methyl-D-aspartic acid-induced neuronal injury in the rat retina.
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.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan. Electronic address: sakamotok@pharm.kitasato-u.ac.jp.
Kenji
K
Sakamoto
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Taiyo
T
Kuroki
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Yui
Y
Okuno
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Haruna
H
Sekiya
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Akihiro
A
Watanabe
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Tomonori
T
Sagawa
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Hiroko
H
Ito
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Aya
A
Mizuta
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Asami
A
Mori
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Tsutomu
T
Nakahara
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan.
Kunio
K
Ishii
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D007274:Injections, Intraperitoneal; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000633:toxicity*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050916:TRPV Cation Channels / Q000819:agonists*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
C530925:1-(2-(1-adamantyl)ethyl)-1-pentyl-3-(3-(4-pyridyl)propyl)urea; D011725:Pyridines; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C527701:enhanced cyan fluorescent protein; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D014508:Urea; D002211:Capsaicin
CGRP (8–37) (PubChem CID: 16134896); Calcitonin gene-related peptide (PubChem CID: 44563440); Capsaicin; Capsaicin (PubChem CID: 1548943); Capsazepine (PubChem CID: 2733484); N-methyl-d-aspartic acid; N-methyl-d-aspartic acid (PubChem CID: 22880); Retina; Substance P (PubChem CID: 36511); Transient receptor potential vanilloid type1