Journal
JOURNAL OF NEUROSCIENCE
Volume 33, Issue 33, Pages 13475-13483Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0419-13.2013
Keywords
-
Categories
Funding
- NEI [5P30EY019007]
- NCI [5P30CA013696]
- Research to Prevent Blindness, New York, NY
- Department of Defense, Fort Detrick, MD [TS080017-W81XWH-09-1-0575]
- Foundation Fighting Blindness
- Joel Hoffman Scholarship
- Schneeweiss Stem Cell Fund
- Barbara and Donald Jonas Family Fund
- Professor Gertrude Rothschild Stem Cell Initiative
- Tistou and Charlotte Kerstan Foundation
- Bernard Becker Association of University Professors in Ophthalmology Research to Prevent Blindness Award
- American Geriatrics Society
- [R01EY018213]
Ask authors/readers for more resources
The third-most common cause of autosomal recessive retinitis pigmentosa (RP) is due to defective cGMP phosphodiesterase-6 (PDE6). Previous work using viral gene therapy on PDE6-mutant mouse models demonstrated photoreceptors can be rescued if administered before degeneration. However, whether visual function can be rescued after degeneration onset has not been addressed. This is a clinically important question, as newly diagnosed patients exhibit considerable loss of rods and cones in their peripheral retinas. We have generated and characterized a tamoxifen inducible Cre-loxP rescue allele, Pde6b(Stop), which allows us to temporally correct PDE6-deficiency. Whereas untreated mutants exhibit degeneration, activation of Cre-loxP recombination in early embryogenesis produced stable long-term rescue. Reversal at later time-points showed partial long-term or short-lived rescue. Our results suggest stable restoration of retinal function by gene therapy can be achieved if a sufficient number of rods are treated. Because patients are generally diagnosed after extensive loss of rods, the success of clinical trials may depend on identifying patients as early as possible to maximize the number of treatable rods.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available