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Differentiation of murine models of “negative ERG” by single and repetitive light stimuli

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Abstract

Purpose

Marked attenuation of the single-flash electroretinographic (ERG) b-wave in the presence of a normal-amplitude or less-attenuated a-wave is commonly referred to as the “negative ERG.” The purpose of this study was to investigate whether the disparate origins of the negative ERG in three murine models can be discriminated using flickering stimuli.

Methods

Three models were selected: (1) the Nyx nob mouse model of complete congenital stationary night blindness, (2) the oxygen-induced retinopathy (OIR) rat model of retinopathy of prematurity (ROP), and (3) the Rs1 knockout (KO) mouse model of X-linked juvenile retinoschisis. Directly after a dark-adapted, single-flash ERG luminance series, a flicker ERG frequency series (0.5–30 Hz) was performed at a fixed luminance of 0.5 log cd s/m2. This series includes frequency ranges that are dominated by activity in (A) the rod pathways (below 5 Hz), (B) the cone ON-pathway (5–15 Hz), and (C) the cone OFF-pathway (above 15 Hz).

Results

All three models produced markedly attenuated single-flash ERG b-waves. In the Nyx nob mouse, which features postsynaptic deficits in the ON-pathways, the a-wave was normal and flicker responses were attenuated in ranges A and B, but not C. The ROP rat is characterized by inner-retinal ischemia which putatively affects both ON- and OFF-bipolar cell activity; flicker responses were reduced in all ranges (A–C). Notably, the choroid supplies the photoreceptors and is thought to be relatively intact in OIR, an idea supported by the nearly normal a-wave. Finally, in the Rs1 KO mouse, which has documented abnormality of the photoreceptor-bipolar synapse affecting both ON- and OFF-pathways, the flicker responses were attenuated in all ranges (A–C). The a-wave was also attenuated, likely as a consequence to schisms in the photoreceptor layer.

Conclusion

Consideration of both single-flash and flickering ERG responses can discriminate the functional pathology of the negative ERG in these animal models of human disease.

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Funding

The Deutsche Forschungsgemeinschaft Grant KFO 134 (TP4) and the Massachusetts Lions Eye Research Fund provided financial support in the form of research funding. The sponsors had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Schleichstr. 4/3, 72076, Tübingen, Germany

    Naoyuki Tanimoto & Mathias W. Seeliger

  2. Department of Ophthalmology, Boston Children’s Hospital, 300 Longwood Avenue, Fegan 4, Boston, MA, 02115, USA

    James D. Akula & Anne B. Fulton

  3. Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Germany

    Bernhard H. F. Weber

Authors
  1. Naoyuki Tanimoto
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  2. James D. Akula
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  3. Anne B. Fulton
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  4. Bernhard H. F. Weber
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  5. Mathias W. Seeliger
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Corresponding author

Correspondence to Naoyuki Tanimoto.

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This article does not contain any studies with human participants performed by any of the authors.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

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Tanimoto, N., Akula, J.D., Fulton, A.B. et al. Differentiation of murine models of “negative ERG” by single and repetitive light stimuli. Doc Ophthalmol 132, 101–109 (2016). https://doi.org/10.1007/s10633-016-9534-1

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  • DOI: https://doi.org/10.1007/s10633-016-9534-1

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