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Tailoi Chan-Ling, Samyoul Ahn, Mark Koina, Samuel J Adamson, Marconi Barbosa, Louise Baxter, Frank Arfuso, Anthony Logaraj, George Fatseas; Changes in the Radial Peri-papillary Capillaries with aging: the forgotten vascular bed in glaucoma pathogenesis.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3344.
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© ARVO (1962-2015); The Authors (2016-present)
To examine if age-associated changes in the radial peri-papillary capillaries (RPCs) constitute a significant component of glaucoma pathogenesis.
8 human fetal eyes, (8-40 weeks gestation (WG), 4 healthy adult eyes (aged 17 to 33), and 12 aged human eyes (aged 40-86 years) were examined using multiple marker immunohistochemistry (wholemounts and transverse sections) with antibodies against CD34, CD39, GFAP, NG2, αSMA, S100β, and UEA-1 Lectin. Vascular density, astrocyte and pericyte ensheathement, RPC distribution, vascular branching patterns, and CD39 expression were examined using confocal microscopy. RPC ultrastructure was examined using TEM.
RPCs were first evident between 18-22WG, in a narrow rim surrounding the optic nerve head and expanded gradually until birth. However, at birth RPC distribution was limited compared to young adult. RPCs showed complete basal lamina and tight junctions between adjacent VECs and were located within a 45um region from the middle of the NFL and middle of GCL. Pericyte ensheathment was examined ultrastucturally and using NG2 and αSMA IHC. The frequency of pericyte ensheathement was 75% of that observed in the capillaries of the inner retinal vascular bed. Remarkably, astrocytic ensheathement examined both ultrastructurally and with anti-GFAP and S100β IHC showed a very rare occurrence of astrocytic ensheathement. RPC vascular density index (33% at 32 years compared to 20% at 80 years) and distribution decreased markedly with age. Using threshold intensity analysis, we demonstrated that CD39 expression decreased with age. Importantly, many RPC segments became discontinuous and rheology and blood flow was likely impeded in the most aged specimens.
Our novel observation that RPCs have a constitutive paucity of astrocytic ensheathment has implications for their ability to auto-regulate blood flow in response to neuronal activity. Taken together, our data leads us to suggest that the lack of astrocytic-vascular interactions on the RPCs and their marked atrophy in aging compromises their ability to maintain homeostasis and support neuronal function in ‘physiological aging’ and contribute to glaucoma pathogenesis. Our findings show a correlation between decreasing RPC vascular perfusion with aging but does not demonstrate causality between vascular changes and GC loss.
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