title: Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors.
abstract: P2X7-type purinergic receptors are distributed throughout the nervous system where they contribute to physiological and pathological functions. In the retina, this receptor is found in both inner and outer cells including microglia modulating signaling and health of retinal cells. It is involved in retinal neurodegenerative disorders such as retinitis pigmentosa and age-related macular degeneration (AMD). Experimental studies demonstrated that saffron protects photoreceptors from light-induced damage preserving both retinal morphology and visual function and improves retinal flicker sensitivity in AMD patients. To evaluate a possible interaction between saffron and P2X7 receptors (P2X7Rs), different cellular models and experimental approaches were used. We found that saffron positively influences the viability of mouse primary retinal cells and photoreceptor-derived 661W cells exposed to ATP, and reduced the ATP-induced intracellular calcium increase in 661W cells. Similar results were obtained on HEK cells transfected with recombinant rat P2X7R but not on cells transfected with rat P2X2R. Finally, patch-clamp experiments showed that saffron inhibited cationic currents in HEK-P2X7R cells. These results point out a novel mechanism through which saffron may exert its protective role in neurodegeneration and support the idea that P2X7-mediated calcium signaling may be a crucial therapeutic target in the treatment of neurodegenerative diseases.
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.|Department of Biotechnology and Applied clinical Science, DISCAB, University of L'Aquila, L'Aquila, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Corso
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cavallero
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Baroni
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Garbati
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Prestipino
authors.affiliation: Department of Biotechnology and Applied clinical Science, DISCAB, University of L'Aquila, L'Aquila, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bisti
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nobile
authors.affiliation: National Research Council, Institute of Biophysics, Via De Marini 6, 16149, Genoa, Italy. picco@ge.ibf.cnr.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Picco
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D027622:Crocus; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D010936:Plant Extracts / Q000627:therapeutic use*; D061251:Primary Cell Culture; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects* / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D010936:Plant Extracts; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate
keywords: Neurodegenerative disease; P2X7 receptor; Retinal cells; Saffron