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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Administration, Oral
-
Animals
-
Blindness / drug therapy*
-
Blindness / physiopathology
-
Carrier Proteins
-
Child
-
Disease Models, Animal
-
Diterpenes
-
Eye Proteins
-
Female
-
Humans
-
Male
-
Mice
-
Mice, Knockout
-
Pigment Epithelium of Eye / physiopathology*
-
Proteins / genetics
-
Proteins / physiology*
-
Retinal Degeneration / drug therapy*
-
Retinal Degeneration / metabolism
-
Retinal Degeneration / physiopathology
-
Retinal Rod Photoreceptor Cells / physiopathology
-
Retinaldehyde / administration & dosage
-
Retinaldehyde / metabolism
-
Retinaldehyde / therapeutic use*
-
Retinoids / administration & dosage
-
Retinoids / metabolism
-
Retinoids / therapeutic use
-
Time Factors
-
cis-trans-Isomerases
Substances
-
Carrier Proteins
-
Diterpenes
-
Eye Proteins
-
Proteins
-
Retinoids
-
9-cis-retinal
-
retinoid isomerohydrolase
-
cis-trans-Isomerases
-
Retinaldehyde