title: Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration.
abstract: Experimental studies demonstrated that saffron (Crocus sativus) given as a dietary supplement counteracts the effects of bright continuous light (BCL) exposure in the albino rat retina, preserving both morphology and function and probably acting as a regulator of programmed cell death [1]. The purpose of this study was to ascertain whether the neuroprotective effect of saffron on rat retina exposed to BCL is associated with a modulation of the endocannabinoid system (ECS). To this aim, we used eight experimental groups of Sprague-Dawley rats, of which six were exposed to BCL for 24 hours. Following retinal function evaluation, retinas were quickly removed for biochemical and morphological analyses. Rats were either saffron-prefed or intravitreally injected with selective type-1 (CB1) or type-2 (CB2) cannabinoid receptor antagonists before BCL. Prefeeding and intravitreally injections were combined in two experimental groups before BCL. BCL exposure led to enhanced gene and protein expression of retinal CB1 and CB2 without affecting the other ECS elements. This effect of BCL on CB1 and CB2 was reversed by saffron treatment. Selective CB1 and CB2 antagonists reduced photoreceptor death, preserved morphology and visual function of retina, and mitigated the outer nuclear layer (ONL) damage due to BCL. Of interest, CB2-dependent neuroprotection was more pronounced than that conferred by CB1. These data suggest that BCL modulates only distinct ECS elements like CB1 and CB2, and that saffron and cannabinoid receptors could share the same mechanism in order to afford retinal protection.
authors.affiliation: Biotechnology and Applied Clinical Sciences Department, University of L'Aquila, L'Aquila, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Maccarone
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rapino
authors.affiliation: Biotechnology and Applied Clinical Sciences Department, University of L'Aquila, L'Aquila, Italy.
authors.forename: Darin
authors.initials: D
authors.lastname: Zerti
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: di Tommaso
authors.affiliation: Faculty of Bioscience, University of Teramo, Teramo, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Battista
authors.affiliation: Biotechnology and Applied Clinical Sciences Department, University of L'Aquila, L'Aquila, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Marco
authors.affiliation: Biotechnology and Applied Clinical Sciences Department, University of L'Aquila, L'Aquila, Italy.|ARC Centre of Excellence in Vision Science, John Curtin School of Medical Research, Australian National University, Canberra ACT 0200, Australia.|Interuniversity Consortium "Istituto Nazionale Biostrutture e Biosistemi" (INBB), Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bisti
authors.affiliation: Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.|European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D027622:Crocus / Q000737:chemistry*; D019587:Dietary Supplements; D063388:Endocannabinoids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008027:Light; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D021381:Protein Transport; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D063388:Endocannabinoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2