Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness

Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known a s Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congen ital amaurosis, have no rod photopigment and severely impaired rod physiolo gy. We analyzed retinoid flow in this model and then intervened by using or al 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h. there was formation of rod photopigment a nd dramatic improvement in rod physiology, thus demonstrating that mechanis m-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.