TY - JOUR
T1 - Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness
AU - Van Hooser, J. Preston
AU - Aleman, Tomas S.
AU - He, Yu Guang
AU - Cideciyan, Artur V.
AU - Kuksa, Vladimir
AU - Pittler, Steven J.
AU - Stone, Edwin M.
AU - Jacobson, Samuel G.
AU - Palczewski, Krzysztof
PY - 2000/7/18
Y1 - 2000/7/18
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.150236297
DO - 10.1073/pnas.150236297
M3 - Article
C2 - 10869443
AN - SCOPUS:0034682551
SN - 0027-8424
VL - 97
SP - 8623
EP - 8628
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -