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Hossein Nazari Khanamiri, Cina Karimaghaei, Maxim Ivannikov, Lorenzo Ochoa, Gracie Vargas, Erik J Van Kuijk, Wenbo Zhang, Massoud Motamedi; Differential loss of retinal microvascular layers in Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2020;61(7):906.
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© ARVO (1962-2015); The Authors (2016-present)
Alzheimer’s disease (AD) has a complex pathogenesis and increasing evidence shows that neurovascular dysfunction is a major component of the disease. Retina is an extension of the brain and retinal vascular changes have been shown in patients with AD. However, the nature and distribution of AD- and age-related retinal vascular changes has not been clarified. The aim of this study was to characterize the AD and senescence dependent alterations in retinal vascular layers in a triple transgenic mouse model of AD (3xTg-AD).
Retinal flat preparations from young (2 months old), middle-aged (10-14 months old), and old (18-20 months old) 3xTg-AD and non-transgenic control mice were immunolabelled for collagen IV. Retinal flat mounts were optically cleared and the entire retinal thickness from the inner limiting membrane to the outer nuclear layer was imaged with confocal microscopy. Three to five eyes were included in each group. Vessel length and density, vascular junction number and density, and the number of vascular endpoints were quantified in orthogonal maximum intensity projections of superficial, middle, and deep vascular plexus using AngiTool.
Superficial, middle, and deep vascular plexus attenuate with age in 3xTg-AD and control mice (decreased vascular length, vascular density, and vascular junction density, P<0.05). Within each age group, no difference was noted in total vascular length, vessel density, vascular junction number and density and the number of vessel endpoints in superficial and middle retinal vascular layers between 3xTg-AD and non-transgenic control mice. However, deep retinal vessels attenuated more significantly in 3xTg-AD retina compared to age and sex-matched controls (P<0.05 for Vessel length and density, vascular junction number and density, and the vascular endpoints).
All three superficial, middle and deep retinal vascular layers attenuate with age. However, loss of deep vascular plexus is more prominent in AD model compared to wild-type controls. Noninvasive retinal vascular imaging may be able to detect such differential loss of retinal vasculature in preclinical AD and help to monitor the disease course and response to potential treatments.
This is a 2020 ARVO Annual Meeting abstract.
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