TY - JOUR
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 - 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.
AB - 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.
KW - Critical flicker fusion frequency (CFF)
KW - Electroretinography (ERG)
KW - Photopic response
UR - http://www.scopus.com/inward/record.url?scp=84925287247&partnerID=8YFLogxK
U2 - 10.1007/s10633-014-9458-6
DO - 10.1007/s10633-014-9458-6
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C2 - 25204753
AN - SCOPUS:84925287247
SN - 0012-4486
VL - 129
SP - 141
EP - 150
JO - Documenta Ophthalmologica
JF - Documenta Ophthalmologica
IS - 3
ER -