title: A novel free radical scavenger rescues retinal cells in vivo.
abstract: The benzopyran BP (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran) is a free radical scavenger that is structurally similar to alpha-tocopherol and has provided neuro-protection in a number of disease models where oxidative stress is a causative factor. A novel derivative of BP with improved lipid solubility, which we have designated BP3, was synthesized and its neuro-protective efficacy subsequently analyzed in three mouse models of retinal disease in vivo. In the acute light damage model, balb/c mice received a single intra-peritoneal injection (200 mg/kg) of BP3 one hour prior to phototoxicity, reducing photoreceptor degeneration for up to 48 h post insult. In the rd10/rd10 mouse, a chronic model of inherited retinal degeneration, systemic dosing with BP3 on alternate days between post-natal day 18 and 25 preserved rod photoreceptor numbers and cone photoreceptor morphology. Finally, NMDA induced toxicity in retinal ganglion cells was diminished for at least 72 h after the initial insult by a single dose of BP3. In each disease model, BP3 alleviated cellular oxidative burden as MDA levels were markedly reduced. These results demonstrate that systemically administered BP3 has potent free radical scavenging capacity in the retina and may represent a single therapeutic strategy applicable across several retinopathies.
authors.affiliation: Cell Development and Disease Laboratory, Biochemistry Department, Bioscience Research Institute, University College Cork, Cork, Ireland. carolyn.omahony@ucc.ie
authors.forename: Carolyn
authors.initials: C
authors.lastname: O'Driscoll
authors.forename: Francesca
authors.initials: F
authors.lastname: Doonan
authors.forename: Nuria
authors.initials: N
authors.lastname: Sanvicens
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Cotter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002452:Cell Count; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D058449:Intravitreal Injections; D008027:Light / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000633:toxicity; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017382:Reactive Oxygen Species; D012160:Retina / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D001578:Benzopyrans; C120400:CR 6; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013481:Superoxides; D008315:Malondialdehyde; D016202:N-Methylaspartate