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Tomoyo Imamura, Yuta Ohno, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara; The role of Cannabinoid receptors on light-induced photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5011.
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Cannabinoid receptors are known as G protein-coupled receptors and classified in CB1 receptor and CB2 receptor. CB1 receptor is mainly localization in the presynaptic terminal of neurons, and regulates the release of neurotransmitters. In contrast, CB2 receptors are expressed in the peripheral nervous system and organs, such as tonsils, spleen, these are involved in the regulation of inflammation and immune response. It has been reported that cannabinoid receptors are related to some neurodegenerative diseases, and expressed in retina. However, the role of cannabinoid receptors in retina remains to be elucidated. Here, we investigated the role of cannabinoid receptors in light-induced photoreceptor degeneration, which is associated with retinitis pigmentosa and age-related macular degeneration.
An murine photoreceptor cell line, 661W, was irradiated by white light at 2,500 lx. To examine the effect of CB1 and CB2 receptors on light-induced retinal cell death, we used each receptors agonist and antagonist, and evaluated cell viability by nuclear staining with propidium iodine and Hoechst33342. In addition, 8 weeks old male ddY mice were induced retinal damage by white light irradiation at 8,000 lx illumination for 3 hours after the dark adaptation for 24 hours. To determine the expression of CB1 and CB2 receptor after light exposure, time-dependent changes of expression level and localization in retina and in 661W cells were measured by Western blotting and immunostaining.
CB1 and CB2 receptors existed in all layers of the retina. Furthermore, the expression level of CB1 receptor was increased by light irradiation, whereas that of CB2 receptor was decreased. In addition, SR141617A, a CB1 receptor antagonist, showed a significant protective effect. On the other hand, HU-308, a CB2 receptor agonist, showed a significant protective effect, whereas SR144528, which is a CB2 antagonist, did not show a clear effect.
CB1 receptor antagonist showed a significant protective effect, whereas a CB2 receptor agonist showed a significant protective effect. Furthermore, the expression level of CB1 and CB2 receptor was changed in light retinal degeneration model. These results suggest that cannnabinoid receptors may be involved in the pathogenesis of retinal diseases such as retinitis pigmentosa and age-related macular degeneration.
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