title: Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness.
abstract: Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.
authors.affiliation: Departments of Ophthalmology, Chemistry, and Pharmacology, University of Washington, Seattle, WA 98195, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Van Hooser
authors.forename: T S
authors.initials: TS
authors.lastname: Aleman
authors.forename: Y G
authors.initials: YG
authors.lastname: He
authors.forename: A V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: V
authors.initials: V
authors.lastname: Kuksa
authors.forename: S J
authors.initials: SJ
authors.lastname: Pittler
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: K
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001766:Blindness / Q000188:drug therapy* / Q000503:physiopathology; D002352:Carrier Proteins; D002648:Child; D004195:Disease Models, Animal; D004224:Diterpenes; D005136:Eye Proteins; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010857:Pigment Epithelium of Eye / Q000503:physiopathology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D012172:Retinaldehyde / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D012176:Retinoids / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D013997:Time Factors; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D004224:Diterpenes; D005136:Eye Proteins; D011506:Proteins; D012172:Retinaldehyde; D012176:Retinoids; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C031390:9-cis-retinal