June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Diminished light adaptation effect seen in cone-driven responses in GRK1-associated Oguchi disease: evidence for possible rod input to cone adaptation pathways
Author Affiliations & Notes
  • ZIHE XU
    Department of Ophthalmology, King’s College London, St Thomas’ Hospital Campus, London, ENGLAND, United Kingdom
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Xiaofan Jiang
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, King’s College London, St Thomas’ Hospital Campus, London, ENGLAND, United Kingdom
  • James Bellingham
    Institute of Ophthalmology, University College London, London, United Kingdom
    Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
  • Zakariya Jarrar
    Department of Ophthalmology, King’s College London, St Thomas’ Hospital Campus, London, ENGLAND, United Kingdom
    Department of Ophthalmology, Guy’s & St Thomas’ NHS Foundation Trust, London, United Kingdom
  • Christopher Hammond
    Department of Ophthalmology, King’s College London, St Thomas’ Hospital Campus, London, ENGLAND, United Kingdom
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Andrew R. Webster
    Institute of Ophthalmology, University College London, London, United Kingdom
    Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
  • Nigel Davies
    Department of Ophthalmology, Guy’s & St Thomas’ NHS Foundation Trust, London, United Kingdom
  • Moin Mohamed
    Department of Ophthalmology, Guy’s & St Thomas’ NHS Foundation Trust, London, United Kingdom
  • Gavin Arno
    Institute of Ophthalmology, University College London, London, United Kingdom
    Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
  • Pirro G Hysi
    Department of Ophthalmology, King’s College London, St Thomas’ Hospital Campus, London, ENGLAND, United Kingdom
  • Omar Abdul Rahman Mahroo
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, King’s College London, St Thomas’ Hospital Campus, London, ENGLAND, United Kingdom
  • Footnotes
    Commercial Relationships   ZIHE XU, None; Xiaofan Jiang, None; James Bellingham, None; Zakariya Jarrar, None; Christopher Hammond, None; Andrew Webster, None; Nigel Davies, None; Moin Mohamed, None; Gavin Arno, None; Pirro Hysi, None; Omar Mahroo, None
  • Footnotes
    Support  Wellcome Trust (206619/Z/17/Z); Fight for Sight UK (1409/10); Moorfields Eye Charity; NIHR Biomedical Research Centre at Moorfields Eye Hospital and the UCL Institute of Ophthalmology.; NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 5052. 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, James Bellingham, Zakariya Jarrar, Christopher Hammond, Andrew R. Webster, Nigel Davies, Moin Mohamed, Gavin Arno, Pirro G Hysi, Omar Abdul Rahman Mahroo; Diminished light adaptation effect seen in cone-driven responses in GRK1-associated Oguchi disease: evidence for possible rod input to cone adaptation pathways. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5052.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The Light Adaptation Effect (LAE) refers to the growth in amplitude, over several minutes, of electroretinogram (ERG) responses to flashes delivered in the presence of a photopic background following prior dark adaptation. It is not known whether rod-driven mechanisms contribute. We investigated this effect in a patient in whom the light-sensitive rod outer segment current was permanently abolished due to constitutive activation of phototransduction.

Methods : A 36 year old patient with a clinical diagnosis of Oguchi disease underwent international standard ERG testing and also the following experimental electrophysiological protocol. The patient dark adapted for 20 minutes and was then exposed to a standard white background (30 cd m-2). White flashes (3 cd m-2 s) were delivered (in groups of 36 flashes, repeated every 2 minutes) for the next 20 minutes. Pupils were pharmacologically dilated and responses recorded using conductive fibre electrodes. Responses were compared with those obtained in identical protocols from 8 healthy subjects (aged 21-39).

Results : International standard electrophysiological testing in the patient showed reduced dark-adapted responses and light-adapted responses that were within normal limits. Genetic screening revealed no pathogenic variants in SAG (encoding the protein arrestin), but novel heterozygous mutations in GRK1 (encoding rhodopsin kinase) were observed. For the experimental ERG protocol, in the healthy subjects, the b-wave amplitude approximately doubled over the recording period, with a median increase in amplitude of 90%. In the patient, the amplitude increased by less than 15% in both eyes.

Conclusions : The patient showed a markedly diminished LAE compared with healthy volunteers. We hypothesise that this was due to constitutively abolished rod outer segment current (with consequent rod hyperpolarisation) in both light and dark, and suggests that in healthy subjects, the LAE is driven by changes in rod signalling from dark to light. We have previously found a normal LAE in a patient with unilaterally impaired rod-driven inner retinal signalling, and speculate that the relevant rod-driven signals might input into the cone pathway at an earlier stage possibly via gap junctions between photoreceptors.

This is a 2020 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.

×