title: Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation.
abstract: OBJECTIVE
  Recently we reported on day blindness in sheep caused by a mutation in the CNGA3 gene, thus making affected sheep a naturally occurring large animal model for therapeutic intervention in CNGA3 achromatopsia patients. The purpose of this study was to characterize flicker cone function in normal and day blind sheep, with the aim of generating a normative data base for ongoing gene therapy studies.
  
  
  METHODS
  Electoretinographic (ERG) cone responses were evoked with full-field conditions in 10 normal, 6 heterozygous carriers and 36 day blind sheep. Following light adaptation (10 min, 30 cd/m(2)), responses were recorded at four increasing light intensities (1, 2.5, 5 and 10 cd s/m(2)). At each of these intensities, a single photopic flash response followed by 8 cone flicker responses (10-80 Hz) was recorded. Results were used to generate a normative data base for the three groups. Differences between day blind and normal control animals were tested in two age-matched groups (n = 10 per group).
  
  
  RESULTS
  The normal sheep cone ERG wave is bipartite in nature, with critical flicker fusion frequency (CFF) >80 Hz. In all four flash intensities, the single photopic flash a-wave and b-wave amplitudes were significantly lower (p < 0.005), and implicit times significantly delayed (p < 0.0001), in day blind animals. In all four flash intensities, CFF values were significantly lower (p < 0.0001) in day blind sheep.
  
  
  CONCLUSIONS
  Cone function is severely depressed in day blind sheep. Our results will provide a normative data base for ongoing gene therapy studies.
authors.affiliation: Koret School of Veterinary Medicine, Hebrew University of Jerusalem, PO Box 12, 7610001, Rehovot, Israel.
authors.forename: Raaya
authors.initials: R
authors.lastname: Ezra-Elia
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.forename: Hen
authors.initials: H
authors.lastname: Honig
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosov
authors.forename: Alexey
authors.initials: A
authors.lastname: Obolensky
authors.forename: Edward
authors.initials: E
authors.lastname: Averbukh
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: Elisha
authors.initials: E
authors.lastname: Gootwine
authors.forename: Ron
authors.initials: R
authors.lastname: Ofri
mesh_terms: D000221:Adaptation, Ocular; D000818:Animals; D003117:Color Vision Defects / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004195:Disease Models, Animal; D004596:Electroretinography / Q000662:veterinary; D005260:Female; D005425:Flicker Fusion / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics / Q000503:physiopathology*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels