Elucidating the role of inner blood retina barrier integrity in the development of dry AMD

Abstract

Purpose : The initiating pathophysiological events in the development of early AMD still remain unclear. Inner blood retina barrier integrity in young, healthy adult humans has been shown to cycle in a circadian manner, mirroring tight junction protein claudin-5 cycling. As circadian rhythm disturbance has previously been associated with other neurodegenerative disorders, we conducted a case controlled observational study to test the hypothesis that inner blood retina barrier circadian kinesis is arrested in AMD patients.

Methods : Patients with AMD over the age of 65 (n=16) and age matched controls (n=11) were recruited and informed consent obtained. Participant’s chronotype was established by way of the Munich Chronotype Questionnaire (MCTQ). Time points in the morning and evening were defined and OCT, FFA and fundal photos were performed. Quantification of FFA images was performed by a bespoke MatLab based software platform. These findings are part of a longitudinal study named the “Irish Circadian Retina Project” which is still recruiting participants with AMD and age matched controls.

Results : In young healthy subjects, 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). Analysis of melatonin and cortisol revealed variations as expected, with cortisol elevated in the morning and melatonin increased in the evening. Upon OCT volume analysis of the macula, no significant differences between AM and PM were observed. Similarly, preliminary data from AMD patients compared to age matched controls suggests a region-dependent fluorescein signal differential, with a more prolonged signal in AMD patients.

Conclusions : The preliminary findings of this study suggest that the iBRB is highly dynamic. We have previously demonstrated the potential size-selective passive diffusion from the inner retinal vasculature to the retinal parenchyma with diffusion towards the outer retina and RPE in young, healthy controls. Now, we have demonstrated that this phenomenon appears to be attenuated with age and absent in AMD patients. We suggest that disruption in the circadian mediated integrity of the iBRB may be an early initiating event in AMD development and progression. To our knowledge, this is the first time the iBRB has been implicated in AMD pathogenesis.

This is a 2021 ARVO Annual Meeting abstract.