Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness
- J. Preston Van Hooser*,
- Tomas S. Aleman†,
- Yu-Guang He*,
- Artur V. Cideciyan†,
- Vladimir Kuksa*,
- Steven J. Pittler‡,
- Edwin M. Stone§,
- Samuel G. Jacobson†, and
- Krzysztof Palczewski*¶‖**
- Departments of *Ophthalmology, ¶Chemistry, and ‖Pharmacology, University of Washington, Seattle, WA 98195; †Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104; ‡Vision Science Research Center, University of Alabama, Birmingham, AL 35294; and §University of Iowa Hospitals and Clinics, Department of Ophthalmology, Iowa City, IA 52242
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Communicated by Hans Neurath, University of Washington, Seattle, WA (received for review May 8, 2000)
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.
Footnotes
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↵** To whom reprint requests should be addressed. E-mail: palczews{at}u.washington.edu.
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Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.150236297.
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Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.150236297
Abbreviations
- LCA,
- Leber congenital amaurosis;
- ROS,
- rod outer segment;
- RPE,
- retinal pigment epithelial cells;
- ERG,
- electroretinogram;
- OCT,
- optical coherence tomography
- Received May 8, 2000.
- Accepted May 22, 2000.
- Copyright © The National Academy of Sciences
