Document Detail

RPE65 gene therapy slows cone loss in Rpe65-deficient dogs.
MedLine Citation:
PMID:  22951453     Owner:  NLM     Status:  MEDLINE    
Recent clinical trials of retinal pigment epithelium gene (RPE65) supplementation therapy in Leber congenital amaurosis type 2 patients have demonstrated improvements in rod and cone function, but it may be some years before the effects of therapy on photoreceptor survival become apparent. The Rpe65-deficient dog is a very useful pre-clinical model in which to test efficacy of therapies, because the dog has a retina with a high degree of similarity to that of humans. In this study, we evaluated the effect of RPE65 gene therapy on photoreceptor survival in order to predict the potential benefit and limitations of therapy in patients. We examined the retinas of Rpe65-deficient dogs after RPE65 gene therapy to evaluate the preservation of rods and cone photoreceptor subtypes. We found that gene therapy preserves both rods and cones. While the moderate loss of rods in the Rpe65-deficient dog retina is slowed by gene therapy, S-cones are lost extensively and gene therapy can prevent that loss, although only within the treated area. Although LM-cones are not lost extensively, cone opsin mislocalization indicates that they are stressed, and this can be partially reversed by gene therapy. Our results suggest that gene therapy may be able to slow cone degeneration in patients if intervention is sufficiently early and also that it is probably important to treat the macula in order to preserve central function.
F M Mowat; A R Breuwer; J T Bartoe; M J Annear; Z Zhang; A J Smith; J W B Bainbridge; S M Petersen-Jones; R R Ali
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-06
Journal Detail:
Title:  Gene therapy     Volume:  20     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-09     Completed Date:  2013-11-01     Revised Date:  2014-03-14    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  545-55     Citation Subset:  IM    
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MeSH Terms
Cell Survival / genetics
Disease Models, Animal
Genetic Therapy
Leber Congenital Amaurosis / genetics,  pathology,  therapy*
Retina / drug effects,  pathology
Retinal Cone Photoreceptor Cells* / drug effects,  pathology
Retinal Rod Photoreceptor Cells* / drug effects,  pathology
cis-trans-Isomerases / administration & dosage,  deficiency,  genetics*
Grant Support
MR/J005215/1//Medical Research Council; NIHR-RP-011-003//Department of Health
Reg. No./Substance:
EC isomerohydrolase; EC 5.2.-/cis-trans-Isomerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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