title: Intravitreal injection of AAV2 transduces macaque inner retina.
abstract: OBJECTIVE
  Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized morphology of the high-acuity human fovea. This was a study of inner retina transduction in the macaque, a primate with ocular characteristics most similar to that of humans.
  
  
  METHODS
  In vivo imaging and histology were used to examine GFP expression in the macaque inner retina after intravitreal injection of AAV vectors containing five distinct promoters.
  
  
  RESULTS
  AAV2 produced pronounced GFP expression in inner retinal cells of the fovea, no expression in the central retina beyond the fovea, and variable expression in the peripheral retina. AAV2 vector incorporating the neuronal promoter human connexin 36 (hCx36) transduced ganglion cells within a dense annulus around the fovea center, whereas AAV2 containing the ubiquitous promoter hybrid cytomegalovirus (CMV) enhancer/chicken-β-actin (CBA) transduced both Müller and ganglion cells in a dense circular disc centered on the fovea. With three shorter promoters--human synapsin (hSYN) and the shortened CBA and hCx36 promoters (smCBA and hCx36sh)--AAV2 produced visible transduction, as seen in fundus images, only when the retina was altered by ganglion cell loss or enzymatic vitreolysis.
  
  
  CONCLUSIONS
  The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea.
authors.affiliation: Flaum Eye Institute, Rochester, New York, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Yin
authors.forename: Kenneth
authors.initials: K
authors.lastname: Greenberg
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hunter
authors.forename: Deniz
authors.initials: D
authors.lastname: Dalkara
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Kolstad
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Masella
authors.forename: Robert
authors.initials: R
authors.lastname: Wolfe
authors.forename: Meike
authors.initials: M
authors.lastname: Visel
authors.forename: Daniel
authors.initials: D
authors.lastname: Stone
authors.forename: Richard T
authors.initials: RT
authors.lastname: Libby
authors.forename: David
authors.initials: D
authors.lastname: Diloreto
authors.forename: David
authors.initials: D
authors.lastname: Schaffer
authors.forename: John
authors.initials: J
authors.lastname: Flannery
authors.forename: David R
authors.initials: DR
authors.lastname: Williams
authors.forename: William H
authors.initials: WH
authors.lastname: Merigan
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism; D017630:Connexins / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics*; D058449:Intravitreal Injections; D008251:Macaca; D017628:Microglia / Q000378:metabolism*; D018613:Microscopy, Confocal; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D016704:Synapsins / Q000235:genetics; D014161:Transduction, Genetic; D000097004:Gap Junction delta-2 Protein
chemical_list: D000199:Actins; D017630:Connexins; D049452:Green Fluorescent Proteins; D016704:Synapsins; D000097004:Gap Junction delta-2 Protein