June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Associations between myopia risk variants and retinal electrophysiological parameters: a role of KCNQ5 in myopia development
Author Affiliations & Notes
  • ZIHE XU
    King's College London Section of Ophthalmology, London, London, United Kingdom
    King's College London Department of Twin Research and Genetic Epidemiology, London, London, United Kingdom
  • Xiaofan Jiang
    University College London Institute of Ophthalmology, London, London, United Kingdom
    King's College London Section of Ophthalmology, London, London, United Kingdom
  • Christopher J Hammond
    King's College London Section of Ophthalmology, London, London, United Kingdom
    King's College London Department of Twin Research and Genetic Epidemiology, London, London, United Kingdom
  • Omar Abdul Rahman Mahroo
    University College London Institute of Ophthalmology, London, London, United Kingdom
    King's College London Section of Ophthalmology, London, London, United Kingdom
  • Pirro G Hysi
    King's College London Section of Ophthalmology, London, London, United Kingdom
    King's College London Department of Twin Research and Genetic Epidemiology, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   ZIHE XU, None; Xiaofan Jiang, None; Christopher Hammond, None; Omar Mahroo, None; Pirro Hysi, None
  • Footnotes
    Support  Wellcome Trust 206619_Z_17_Z
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2282. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      ZIHE XU, Xiaofan Jiang, Christopher J Hammond, Omar Abdul Rahman Mahroo, Pirro G Hysi; Associations between myopia risk variants and retinal electrophysiological parameters: a role of KCNQ5 in myopia development. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2282.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Numerous myopia risk loci have been identified, but underlying mechanisms remain unclear. Retinal signalling pathways are thought to be involved in controlling refractive development. The electrical responses of retinal neuronal populations can be recorded non-invasively in vivo from human subjects as the electroretinogram (ERG). We investigated associations between myopia risk loci and ERG parameters.

Methods : Adult twins from the TwinsUK cohort underwent ERG recordings incorporating the International Society for Clinical Electrophysiology of Vision (ISCEV) protocol. Recordings were made with conductive fibre electrodes in the lower conjunctival fornix. In participants with genotypic information, we explored associations between ISCEV ERG parameters and allelic dosages of 1361 exonic variants that were previously associated with refractive error. Genetic associations were quantified using univariate linear mixed models, adjusted for age and sex and genetic relatedness between family members. Secondary analyses, adjusting for the strongest known genetic effects in adjacent genomic regions associated with myopia, were used to explore the origin of the association signals in the respective loci.

Results : Genotypic information was available for 187 participants. One candidate risk locus (rs2840795) near the gene KCNQ5, showed the most significant association (p = 7.84 x10-5) with an ISCEV parameter, namely the b-wave peak time elicited in the dark-adapted response to white flashes (3 cd m-2 s). The association remained significant even after adjustment for two additional common known polymorphisms (SNPs) at the KCNQ5 locus. The ERG b-wave response to this stimulus arises in bipolar cells driven by both rod and cone photoreceptors.

Conclusions : The association between the locus at KCNQ5 and ERG b-wave peak time suggest the possibility that changes in patterns of KCNQ5 expression or function might affect the timing of retinal bipolar cell signals generated in response to photoreceptor light-evoked responses. Immunohistochemistry studies in primate retina have shown KCNQ5 in the retinal pigment epithelium and neural retina, including in photoreceptor inner segments, which would be consistent with this effect. It is possible that alterations in bipolar cell responses are involved in conferring susceptibility to myopia.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×