Rimonabant, a selective cannabinoid1receptor antagonist, protects against light-induced retinal degeneration in vitro and in vivo.
The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer's disease. An endogenous constellation of proteins related to cannabinoid1receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid. However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown. Therefore, we investigated involvement of the cannabinoid1receptor in light-induced retinal degeneration using in vitro and in vivo models. To evaluate the effect of cannabinoid1receptors in light irradiation-induced cell death, the mouse retinal cone-cell line (661W) was treated with a cannabinoid1receptor antagonist, rimonabant. Time-dependent changes of expression and localization of retinal cannabinoid1receptors were measured using Western blot and immunostaining. Retinal damage was induced in mice by exposure to light, followed by intravitreal injection of rimonabant. Electroretinograms and histologic analyses were performed. Rimonabant suppressed light-induced photoreceptor cell death. Cannabinoid1receptor expression was upregulated by light exposure. Treatment with rimonabant improved both a- and b-wave amplitudes and the thickness of the outer nuclear layer. These results suggest that the cannabinoid1receptor is involved in light-induced retinal degeneration and it may represent a therapeutic target in the light-induced photoreceptor degeneration related diseases.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: imamura_tomoyo@phm.kracie.co.jp.
Tomoyo
T
Imamura
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: tsuruma.yakkou@gmail.com.
Kazuhiro
K
Tsuruma
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: inoue.yakkou@gmail.com.
Yuki
Y
Inoue
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: otsuka.yakkou@gmail.com.
Tomohiro
T
Otsuka
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: ohno.yakkou@gmail.com.
Yuta
Y
Ohno
Discovery Research Laboratories III, Ono Pharmaceutical Co., Ltd., Osaka, Japan. Electronic address: ohgami@ono.co.jp.
Shiho
S
Ogami
Discovery Research Laboratories III, Ono Pharmaceutical Co., Ltd., Osaka, Japan. Electronic address: s.yamane@ono.co.jp.
Shinsaku
S
Yamane
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: shimazawa@gifu-pu.ac.jp.
Masamitsu
M
Shimazawa
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
Hideaki
H
Hara
D000818:Animals; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077285:Rimonabant
D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000077285:Rimonabant
Age-related macular degeneration; Cannabinoid; Oxidative stress; Photoreceptor; Rimonabant