Abstract
Purpose :
Most research to date on the likely causes of age-related macular degeneration (AMD) focus on dysfunction in the retinal pigment epithelium (RPE) and the outer blood retinal barrier (oBRB). Claudin-5 is a tight junction protein abundantly expressed at the inner blood retinal barrier (iBRB) and absent at the oBRB. The CLDN5 gene, which encodes claudin-5, has been shown to cycle in a circadian manner in the retina. The aim of this comparative study is to determine if the physiological circadian-regulation of iBRB permeability is dysfunctional in early and intermediate dry AMD.
Methods :
Participants with early or intermediate dry AMD, age-matched controls and healthy young participants aged between 18 to 30 years were recruited. Each participant had an optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) performed, both in the morning and evening. Mid-phase fluorescein signal in the macula was quantified using novel Fluorescent Ocular Vascular Analysis Software (FOVAS) and analysed as per the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. The FOVAS-derived median fluorescein signal in the evening was compared to the morning, to assess circadian cycling. Recruitment of participants is ongoing.
Results :
The combined foveal and parafoveal region demonstrated a median fluorescein signal in the evening compared to morning, that was 20 % greater in healthy young participants (n = 33, *p = 0.03), 8 % greater in age-matched controls (n = 15, p = 0.4) and 4 % less in AMD participants (n = 34, p = 0.8).
Conclusions :
iBRB permeability is dynamic and normally follows a circadian pattern. This appears to be reduced in older people without AMD, and is lost or reversed in people with AMD. This suggests that the circadian-dependant regulation of iBRB kinesis decreases with ageing and may be arrested in AMD. We believe that this disruption could be due to decreased or dysfunctional claudin-5 levels resulting in a modulated, "leakier" iBRB, which may be a factor in the development of AMD over a prolonged time period.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.