Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation

Raaya Ezra-Elia, Eyal Banin, Hen Honig, Alexander Rosov, Alexey Obolensky, Edward Averbukh, William W. Hauswirth, Elisha Gootwine, Ron Ofri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Purpose: 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/m2), responses were recorded at four increasing light intensities (1, 2.5, 5 and 10 cd s/m2). 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.

Original languageAmerican English
Pages (from-to)141-150
Number of pages10
JournalDocumenta Ophthalmologica
Volume129
Issue number3
DOIs
StatePublished - 1 Dec 2014

Bibliographical note

Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.

Keywords

  • Critical flicker fusion frequency (CFF)
  • Electroretinography (ERG)
  • Photopic response

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