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Gene Therapy for MERTK-Associated Retinal Degenerations.
Gene Therapy for MERTK-Associated Retinal Degenerations.
- Source :
-
Advances in experimental medicine and biology [Adv Exp Med Biol] 2016; Vol. 854, pp. 487-93. - Publication Year :
- 2016
-
Abstract
- MERTK-associated retinal degenerations are thought to have defects in phagocytosis of shed outer segment membranes by the retinal pigment epithelium (RPE), as do the rodent models of these diseases. We have subretinally injected an RPE-specific AAV2 vector, AAV2-VMD2-hMERTK, to determine whether this would provide long-term photoreceptor rescue in the RCS rat, which it did for up to 6.5 months, the longest time point examined. Moreover, we found phagosomes in the RPE in the rescued regions of RCS retinas soon after the onset of light. The same vector also had a major protective effect in Mertk-null mice, with a concomitant increase in ERG response amplitudes in the vector-injected eyes. These findings suggest that planned clinical trials with this vector will have a favorable outcome.
- Subjects :
- Animals
Bestrophins
Chloride Channels genetics
Dependovirus genetics
Disease Models, Animal
Electroretinography
Eye Proteins genetics
Genetic Vectors genetics
Humans
Mice, Knockout
Phagocytosis genetics
Phagocytosis physiology
Phagosomes metabolism
Promoter Regions, Genetic genetics
Proto-Oncogene Proteins deficiency
Proto-Oncogene Proteins metabolism
Rats, Mutant Strains
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases deficiency
Receptor Protein-Tyrosine Kinases metabolism
Retinal Degeneration physiopathology
Retinal Pigment Epithelium metabolism
Retinal Pigment Epithelium physiopathology
Treatment Outcome
c-Mer Tyrosine Kinase
Genetic Therapy methods
Proto-Oncogene Proteins genetics
Receptor Protein-Tyrosine Kinases genetics
Retinal Degeneration genetics
Retinal Degeneration therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0065-2598
- Volume :
- 854
- Database :
- MEDLINE
- Journal :
- Advances in experimental medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 26427450
- Full Text :
- https://doi.org/10.1007/978-3-319-17121-0_65