June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
ERG Analysis of the Murine GARP2 Knockout: Abnormal Retinal Function
Author Affiliations & Notes
  • Delores A. Stacks
    Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Marci L DeRamus
    Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Carrie E Huisingh
    Ophthalmology, UAB, Birmingham, Alabama, United States
  • Gerald McGwin
    Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Timothy W Kraft
    Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Steven J Pittler
    Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Delores Stacks, None; Marci DeRamus, None; Carrie Huisingh, None; Gerald McGwin, None; Timothy Kraft, None; Steven Pittler, None
  • Footnotes
    Support   NIH R01 EY018143 and NIH P30 EY003039
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 275. doi:
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    • Get Citation

      Delores A. Stacks, Marci L DeRamus, Carrie E Huisingh, Gerald McGwin, Timothy W Kraft, Steven J Pittler; ERG Analysis of the Murine GARP2 Knockout: Abnormal Retinal Function. Invest. Ophthalmol. Vis. Sci. 2017;58(8):275.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glutamic acid-rich protein, GARP2, is the most abundantly expressed of three photoreceptor (PR) proteins encoded by the Cngb1 locus which also encodes GARP1, and the β-subunit of the cyclic nucleotide-gated cation channel. In our GARP2 knockout mice (GARP2-KO), we previously reported changes in the appearance of the retinal pigment epithelium (RPE) including displaced melanosomes and regional perturbations in the PR/RPE interdigitation zone, in which the PR outer segments appear longer and parallel to the RPE microvillus processes. Here, we tested for electrophysiological consequences of the observed morphologic changes.

Methods : All testing was done on 3-month-old WT (n=8) and GARP2-KO (n=9) mice on a C57Bl/6J background. Functional testing included scotopic ERG with increasing flash intensities, photopic ERG to a saturating flash, scotopic and photopic flicker ERG, and scotopic c-wave. Phototransduction gain, critical flicker fusion threshold (CFF), stimulus required to evoke half maximum response (I50), and c-wave area analyses were performed in IgorPro 6 with Wilcoxon ranked sum statistics performed with SAS software (significance p ≤ 0.05).

Results : Scotopic a- and b- waves were reduced 33% and 50% respectively in the GARP2-KO (a: 256±91 µV, b: 499±183 µV) compared to WT (a:384±112 µV, b: 990±225 µV). Photopic a- and b-waves were also reduced (a: GARP2-KO 128±51 µV, WT 208±68 µV; b: GARP2-KO 168±59 µV, WT 428±128 µV). Assuming linearity between b-wave amplitude and area under the c-wave curve, a significant reduction in c-wave was observed in the GARP2-KO for two scotopic intensities (by 23% and 28% respectively). Scotopic CFF was reduced by 29.4% in GARP2-KO (15.1 ± 1.4 Hz) vs WT (21.4 ± 2.6 Hz). No significant changes were observed in gain, photopic CFF, or the I50.

Conclusions : Our results are consistent with a GARP2 role in modulating PR responses. Although there is likely some damage to the cone-driven circuits (loss of photopic a-, and b-wave maximum amplitudes) the threshold detection of flicker (photopic CFF) is maintained. The rod signaling pathway seems to be more affected, indicated by the significantly reduced scotopic CFF. Reduced c-waves in the GARP2-KO indicate that GARP2 may also affect RPE/PR potassium ion flow, particularly under conditions where the PR response is primarily rod-driven.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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