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Aisling Naylor, Natalie Hudson, Alan Hopkins, Sarah Doyle, Mark Cahill, Matthew Campbell; Inner blood retinal barrier (iBRB) integrity exhibits circadian medicated cycling in human subjects. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2643.
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The relationship between iBRB permeability, the circadian clock and the development of age-related macular degeneration (AMD) is unknown. To assess retinal vascular integrity changes we performed quantitative fundus fluorescein angiography (FFA) and screened peripheral blood samples from AM and PM for circadian markers in healthy human subjects and AMD patients. Our results demonstrate a significant increase and more prolonged fluorescein signal in the evening compared to the morning in healthy volunteers. To continue this research we are now recruiting and expanding the study to include participants with early AMD and age-matched controls.
Healthy human volunteers aged 18-30 were recruited, informed consent was obtained from all participants. Fundus colour photography, optical coherence tomography (OCT) and FFA were performed at defined time points in the AM and PM. The chronotype of each participant was determined using the Munich Chronotype Questionnaire (MCTQ). Peripheral blood samples were screened for circadian markers, which included ELISA analysis of serum cortisol and melatonin and evaluation of RNA levels of BMAL-1, Per2 and Rev-Erbα in peripheral blood mononuclear cells (PBMCs). ImageJ analysis was used for quantification of FFA images with the macula divided into the central fovea, inner macula and outer macula regions.
Fluorescein signal was evident and more prolonged in the evening compared to the morning and this was significantly increased in the inner macula***, outer macula *** and total area**(n=33 subjects, ***p<0.0005, **p <0.0026). As expected cortisol levels were elevated in the morning and melatonin in the evening. No significant differences between AM and PM were observed when macular OCT volume was assessed.
Our study demonstrates that the iBRB is highly dynamic. FFA analysis shows a more permeable iBRB in the evening compared to the morning within the same individual. This indicates a systemically injected tracer molecule undergoes a potential size-selective passive diffusion from the inner retinal vasculature to the retinal parenchyma with diffusion towards the outer retina and RPE. This finding may represent a critically important physiological process central to the development of AMD. We propose that disruption in the circadian mediated integrity of the iBRB may be an early initiating factor in AMD development and progression.
This is a 2020 ARVO Annual Meeting abstract.
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