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

doi:10.1007/s10633-014-9458-6

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

The Koret School of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

19 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 language	American English
Pages (from-to)	141-150
Number of pages	10
Journal	Documenta Ophthalmologica
Volume	129
Issue number	3
DOIs	https://doi.org/10.1007/s10633-014-9458-6
State	Published - 1 Dec 2014

Bibliographical note

Funding Information:
Acknowledgments This study was supported (in part) by Grant No. 3-00000-8290 from the Chief Scientist Office of the Ministry of Health, Israel, and by Grant No. 2011445 from the U.S.-Israel Binational Science Foundation, as well as unrestricted awards from The Joseph Alexander Foundation, Yedidut 1 Research Grant and Macula Vision Research Foundation. The authors thank Tali Bdolah-Abram for her help with statistical analysis of the data.

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

Keywords

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

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10.1007/s10633-014-9458-6

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@article{6e38aa193e354ad5bfc64c06648c21d0,

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

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.",

keywords = "Critical flicker fusion frequency (CFF), Electroretinography (ERG), Photopic response",

author = "Raaya Ezra-Elia and Eyal Banin and Hen Honig and Alexander Rosov and Alexey Obolensky and Edward Averbukh and Hauswirth, {William W.} and Elisha Gootwine and Ron Ofri",

note = "Funding Information: Acknowledgments This study was supported (in part) by Grant No. 3-00000-8290 from the Chief Scientist Office of the Ministry of Health, Israel, and by Grant No. 2011445 from the U.S.-Israel Binational Science Foundation, as well as unrestricted awards from The Joseph Alexander Foundation, Yedidut 1 Research Grant and Macula Vision Research Foundation. The authors thank Tali Bdolah-Abram for her help with statistical analysis of the data. Publisher Copyright: {\textcopyright} 2014, Springer-Verlag Berlin Heidelberg.",

year = "2014",

month = dec,

day = "1",

doi = "10.1007/s10633-014-9458-6",

language = "American English",

volume = "129",

pages = "141--150",

journal = "Documenta Ophthalmologica",

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T1 - Flicker cone function in normal and day blind sheep

T2 - a large animal model for human achromatopsia caused by CNGA3 mutation

AU - Ezra-Elia, Raaya

AU - Banin, Eyal

AU - Honig, Hen

AU - Rosov, Alexander

AU - Obolensky, Alexey

AU - Averbukh, Edward

AU - Hauswirth, William W.

AU - Gootwine, Elisha

AU - Ofri, Ron

N1 - Funding Information: Acknowledgments This study was supported (in part) by Grant No. 3-00000-8290 from the Chief Scientist Office of the Ministry of Health, Israel, and by Grant No. 2011445 from the U.S.-Israel Binational Science Foundation, as well as unrestricted awards from The Joseph Alexander Foundation, Yedidut 1 Research Grant and Macula Vision Research Foundation. The authors thank Tali Bdolah-Abram for her help with statistical analysis of the data. Publisher Copyright: © 2014, Springer-Verlag Berlin Heidelberg.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

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KW - Critical flicker fusion frequency (CFF)

KW - Electroretinography (ERG)

KW - Photopic response

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SN - 0012-4486

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ER -

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

Abstract

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Keywords

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