title: Gene Therapy for MERTK-Associated Retinal Degenerations.
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.
authors.affiliation: Beckman Vision Center, UCSF School of Medicine, 10 Koret Way, 94143-0730, San Francisco, CA, USA. matthew.lavail@ucsf.edu.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: LaVail
authors.affiliation: Beckman Vision Center, UCSF School of Medicine, 10 Koret Way, 94143-0730, San Francisco, CA, USA. matthew.lavail@ucsf.edu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Yasumura
authors.affiliation: Beckman Vision Center, UCSF School of Medicine, 10 Koret Way, 94143-0730, San Francisco, CA, USA. Michael.Matthes@ucsf.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Matthes
authors.affiliation: Beckman Vision Center, UCSF School of Medicine, 10 Koret Way, 94143-0730, San Francisco, CA, USA. yang.harvey@gmail.com.
authors.forename: Haidong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, 32610-0284, Gainesville, FL, USA. hauswrth@ufl.edu.
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, 32610-0284, Gainesville, FL, USA.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Deng
authors.affiliation: Department of Genetics, Stanford University School of Medicine, 94305, Stanford, CA, USA. Vollrath@stanford.edu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Vollrath
mesh_terms: D000818:Animals; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D000076202:c-Mer Tyrosine Kinase
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; C490767:Mertk protein, mouse; C490765:Mertk protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase
keywords: Gene therapy; MERTK; Phagocytosis; Retinal degeneration; Treatment