Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy.
Mutations in the beta subunit of the cGMP phosphodiesterase gene (beta PDE) can cause a recessively inherited retinal degeneration in several species, including mice, dogs and humans. We tested the possibility of altering the course of retinal degeneration in the rd mouse through subretinal injection of a recombinant replication-defective adenovirus that contains the murine cDNA for wild-type (beta PDE, Ad.CMV beta PDE. Subretinal injection of Ad.CMV beta PDE results in beta PDE transcripts and increased PDE activity and delays photoreceptor cell death by six weeks. The findings demonstrate cell rescue by in vivo gene transfer, thus supporting the feasibility of treating an inherited retinal degeneration by somatic gene therapy.
Bennett
J
J
Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA.
Tanabe
T
T
Sun
D
D
Zeng
Y
Y
Kjeldbye
H
H
Gouras
P
P
Maguire
A M
AM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000256:Adenoviridae / Q000737:chemistry / Q000235:genetics; D000818:Animals; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D003587:Cytomegalovirus / Q000235:genetics; D004195:Disease Models, Animal; D005123:Eye / Q000187:drug effects; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D006720:Homozygote; D007267:Injections; D051379:Mice; D008815:Mice, Inbred Strains; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D012160:Retina / Q000033:anatomy & histology / Q000187:drug effects; D012162:Retinal Degeneration / Q000235:genetics* / Q000628:therapy*; D014018:Tissue Distribution
D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3