June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Circadian regulation of the inner blood retinal barrier: a paradigm for dry age-related macular degeneration development
Author Affiliations & Notes
  • Fionn O'Leary
    Smurfit Institute of Genetics Trinity College, Dublin, Ireland
    Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  • Natalie Hudson
    Smurfit Institute of Genetics Trinity College, Dublin, Ireland
  • Jeffrey O'Callaghan
    Smurfit Institute of Genetics Trinity College, Dublin, Ireland
  • Matthew Campbell
    Smurfit Institute of Genetics Trinity College, Dublin, Ireland
  • Mark Cahill
    Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  • Footnotes
    Commercial Relationships   Fionn O'Leary None; Natalie Hudson None; Jeffrey O'Callaghan None; Matthew Campbell None; Mark Cahill None
  • Footnotes
    Support  European Research Council (ERC) grant, ‘Retina-Rhythm’ (864522)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 347 – F0178. doi:
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      Fionn O'Leary, Natalie Hudson, Jeffrey O'Callaghan, Matthew Campbell, Mark Cahill; Circadian regulation of the inner blood retinal barrier: a paradigm for dry age-related macular degeneration development. Invest. Ophthalmol. Vis. Sci. 2022;63(7):347 – F0178.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) is divided into an atrophic (dry) and neovascular (wet) form. The disease aetiology is yet to be fully elucidated and no effective treatment exists for the end stage of dry AMD, known as geographic atrophy. We have shown that the inner blood retinal barrier (iBRB) cycles in a circadian manner in young healthy adult controls. The tight junction protein claudin-5 which cycles in a circadian manner, is thought to be central to the maintenance of iBRB integrity. We performed a case control study to determine the circadian effect on iBRB kinesis in AMD.

Methods : Participants with dry AMD (n=19) and age matched controls (n=12) were recruited. The Munich Chronotype Questionnaire was used to establish participant chronotype. Participants were assessed using optical coherence tomography (OCT) and fundus fluorescein angiography (FFA). Mid phase fluorescein signal in the macula was quantified using novel Fluorescent Ocular Vascular Analysis Software and analysed as per the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Fluorescein signal was compared between the morning and the evening for each participant, a proxy for circadian effect on iBRB integrity. Recruitment of participants is ongoing.

Results : There was an increased fluorescein signal throughout all areas of the macula in the evening compared to the morning in young healthy controls (n=30, P =.033). The evening versus morning fluorescein signal differential was reduced and therefore not significant in AMD participants (P =.78). The fluorescein signal appears to persist in the macula longer in AMD participants compared to young healthy controls.

Conclusions : These findings suggest that the iBRB is highly dynamic, with increased fluorescein permeability in the evening compared to the morning in young healthy controls. The circadian associated fluorescein signal differential present in young healthy controls appears attenuated in age matched controls, with no significant difference present in AMD subjects. This suggests that the circadian dependant regulation of iBRB kinesis decreases with ageing and may be arrested in AMD. We suggest that this disruption may be due to decreased or dysfunctional claudin-5 resulting in a more open, "leakier" iBRB, which may be one of the early initiating factors in AMD pathogenesis.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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