title: Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer.
abstract: Retinitis pigmentosa (RP) is the most common inherited retinal disease, in which photoreceptor cells degenerate, leading to blindness. Mutations in the rod photoreceptor cGMP phosphodiesterase beta subunit (PDEbeta) gene are found in patients with autosomal recessive RP as well as in the rd mouse. We have recently shown that lentivirus vectors based on human immunodeficiency virus (HIV) type 1 achieve stable and efficient gene transfer into retinal cells. In this study, we evaluated the potential of HIV vector-mediated gene therapy for RP in the rd mouse. HIV vectors containing a gene encoding a hemagglutinin (HA)-tagged PDEbeta were injected into the subretinal spaces of newborn rd mouse eyes. One to three rows of photoreceptor nuclei were observed in the eyes for at least 24 weeks postinjection, whereas no photoreceptor cells remained in the eyes of control animals at 6 weeks postinjection. Expression of HA-tagged PDEbeta in the rescued photoreceptor cells was confirmed by two-color confocal immunofluorescence analysis using anti-HA and anti-opsin antibodies. HIV vector-mediated gene therapy appears to be a promising means for the treatment of recessive forms of inherited retinal degeneration.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Miyoshi
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
authors.forename: F H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics*; D000818:Animals; D002417:Cattle; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D015497:HIV-1; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D010727:Phosphoric Diester Hydrolases; D017948:Retinal Rod Photoreceptor Cells; D012174:Retinitis Pigmentosa / Q000628:therapy*
chemical_list: D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517431:PDE6B protein, human; C517438:Pde6b protein, mouse