StriatechJournal Club

Developing a Novel Gene Therapy for Kcnv2 Retinopathy

Livia Carvalho, Ph.D. - University of Melbourne

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Mutations in the voltage-gated (Kv) potassium channels Kv8.2 subunit are known to underlie a particular form of inherited irreversible blindness, KCNV2 retinopathy. This unique condition causes lifelong visual loss, characterized by reduced visual acuity, photoaversion, night blindness and abnormal colour vision, and presents phenotypically with a supernormal electrophysiological (ERG) retinal response to light. Livia and colleagues have previously characterised a Kv8.2 knockout mouse model of which accurately mimics the human condition. Their study investigated the suitability of an AAV-based gene therapy approach as a potential treatment. The efficacy of the gene therapy to rescue vision was evaluated via ERG, optomotor testing, histological analysis and single-cell RNASeq. The results show that treatment with either of their vectors was dose-dependent but had a significant impact on the ERG responses. Treated animals also showed recovery to wildtype levels of their scotopic contrast and acuity, and photopic acuity via optomotor responses. Their study is the first to develop and validate the efficacy of a novel gene therapy treatment for KCNV2 retinopathy.

Key Topics

  • What is KCNV2 retinopathy
  • How the knockout mouse model mimics the human condition
  • How a novel gene therapy for this condition was tested
  • The gene replacement therapy is effective and provides improved visual responses

Learning Objectives

Participants will learn what KCNV2 retinopathy is and what causes it. They will also learn how the first mouse model of this disease is characterised, how it mimics the human condition and what were the determining factors that helped the development of a novel gene replacement therapy. Finally, participants will also learn how this new therapy was tested and how efficacy of the treatment was determined.

Background Reading

The origins of the full-field flash electroretinogram b-wave. Bhatt Y, Hunt DM, Carvalho LS.
Front Mol Neurosci. 2023 Jul 3;16:1153934.
doi: 10.3389/fnmol.2023.1153934.

The role of voltage-gated ion channels in visual function and disease in mammalian photoreceptors. Rashwan R, Hunt DM, Carvalho LS.
Pflugers Arch. 2021 Sep;473(9):1455-1468.
doi: 10.1007/s00424-021-02595-2.

Molecular, cellular and functional changes in the retinas of young adult mice lacking the voltage-gated K+ channel subunits Kv8.2 and Kv2.1. Jiang X, Rashwan R, Voigt V, Nerbonne J, Hunt DM, Carvalho LS.
Int J Mol Sci. 2021 May 5;22(9):4877.
doi: 10.3390/ijms22094877.

The role of the voltage-gated potassium channel proteins Kv8.2 and Kv2.1 in vision and retinal disease: insights from the study of mouse gene knock-out mutations. Hart NS, Mountford JK, Voigt V, Fuller-Carter P, Barth M, Nerbonne JM, Hunt DM, Carvalho LS.
eNeuro. 2019 Feb 25;6(1):ENEURO.0032-19.2019.
doi: 10.1523/ENEURO.0032-19.2019.

Synthetic adeno-associated viral vector efficiently targets mouse and non-human primate retina in vivo. Carvalho LS, Xiao R, Wassmer S, Langsdorf A, Zinn E, Pacouret S, Shah S, Comander JI, Kim LA, Lim L, Vandenberghe LH.
Hum Gene Ther. 2018 Jul;29(7):771-784.
doi: 10.1089/hum.2017.154.

About the speaker

Livia Carvalho, Ph.D.

Livia Carvalho, Ph.D.

Senior Lecturer in Optometry & Vision Sciences
University of Melbourne


Dr Livia Carvalho received her PhD from University College London (UCL) in 2009 on the molecular evolution of colour vision and completed two postdoctoral positions at UCL and Harvard Medical School on gene therapy for inherited retinal diseases. From 2014 to 2017 she received an early-career fellowship from the Australian Research Council and started her independent research group at the University of Western Australia/Lions Eye Institute. She has recently started a Senior Lecturer position with the Department of Optometry and Vision Sciences at the University of Melbourne. Her research focuses on understanding cellular and molecular disease mechanisms of inherited retinal diseases and testing of novel gene and drug therapies.

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Journal Club: Developing a Novel Gene Therapy for Kcnv2 Retinopathy
Jan 24th, 2024

    Striatech Journal Club - University of Melbourne

    I already use optomotor measurementsI want to do optomotor measurements in the future

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