July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Role of the voltage-gated potassium channel subunit Kv8.2 in inherited retinal disease and interaction with other channel proteins
Author Affiliations & Notes
  • David M Hunt
    Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia
    School of Biological Sciences, University of Western Australia, Perth, Western Australia, Australia
  • Nathan Hart
    Department of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia
  • Jessica K Mountford
    School of Biological Sciences, University of Western Australia, Perth, Western Australia, Australia
    Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia
  • Melanie Barth
    Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia
  • Paula Fuller-Carter
    Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia
  • Livia S Carvalho
    Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia
  • Footnotes
    Commercial Relationships   David Hunt, None; Nathan Hart, None; Jessica Mountford, None; Melanie Barth, None; Paula Fuller-Carter, None; Livia Carvalho, None
  • Footnotes
    Support  NHMRC Grant 1029740
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2328. doi:
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    • Get Citation

      David M Hunt, Nathan Hart, Jessica K Mountford, Melanie Barth, Paula Fuller-Carter, Livia S Carvalho; Role of the voltage-gated potassium channel subunit Kv8.2 in inherited retinal disease and interaction with other channel proteins. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2328.

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

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Abstract

Purpose : The objective of this study was to assess the role of voltage-gated potassium channels in phototransduction. A unique form of cone-rod dysfunction arises from mutations in the KCNV2 gene which encodes the voltage-gated potassium channel subunit Kv8.2. The ERG shows a severe reduction in a- and b-wave amplitudes at lower light intensities which changes to an enhanced b-wave at higher intensities. Kv8.2 only forms functional channels with another channel protein, Kv2.1, encoded by KCNB1. We now have characterised the retinal phenotype of knock-out (KO) mouse models for both genes and the double KO.

Methods : Mouse KOs for kcnv2 (Kv8.2) and kcnb1 (Kv2.1) were assessed for scotopic and photopic ERG responses. Retinal histology was examined by OCT, cone loss by immunohistochemistry with cone arrestin antibody, cell death by TUNEL, and expression of kcnv2 and kcnb1 by qPCR.

Results : A mild reduction in the overall thickness of retinae of KO mice is due largely to reductions in the outer nuclear and photoreceptor layers. Cell death is also moderately increased in KO mice, with only a 20% loss of cones. The ERG in Kv8.2 KO mice is severely depressed at low flash intensities but flips to an enhanced response at higher intensities. At all intensities, the implicit time for the b-wave is prolonged. The Kv2.1 and double KO mice show similar patterns, although in neither case is there an enhanced response. The a-wave in all three KO lines remains severely depressed, and the c-wave is totally absent. Photopic flicker is also reduced but only marginally delayed.

Conclusions : These results validate the Kv8.2 KO as a good model of the human disorder. Loss of functional Kv2.1 subunits results in a similar phenotype to the Kv8.2 KO, although responses to light flashes remain depressed at all intensities. In both mouse models, the a-wave is severely reduced, and this contributes substantially to the reduced scotopic response. The loss of photoreceptors is mild; this disorder may be a good candidate therefore for gene therapy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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