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Elena Ivanova, Christopher Yee, Botir T Sagdullaev; Remodeling of the blood-retinal barrier in neurodegenerative disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2273.
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© ARVO (1962-2015); The Authors (2016-present)
Adequate blood supply is imperative for retinal function and accomplished by two distinct vascular sources. The outer sensory layer is served by the choroid, which has fenestrated capillaries, while the remaining retina is nourished by the retinal vasculature, which possesses the blood-retinal barrier. In healthy retina, the two circulations are separated by photoreceptors. During the progression of retinal degeneration (RD), the photoreceptors are lost. The purpose of this study was to determine how the choroid and retinal vasculature interact in this degenerative process.
Structural and functional assessment of the vasculature was conducted in the eyecup preparations of rd10 mice, a mouse model of human RD, and age-matched wildtype controls. In living tissue, barrier properties and blood vessels diameter were assessed by Evans Blue. The same preparations were fixed and labeled for structural elements with isolectin and for functional markers with the antibodies for pericytes, albumin, vascular fenestration and the blood-retinal barrier.
In RD retinas, isolectin labeling showed degradation of blood vessels, and up to 60% of the isolectin-labeled blood vessels were not perfused. Furthermore, the perfused blood vessels were constricted. The deep and intermediate retinal vascular layers proximal to degenerating photoreceptors were most affected. The presence of fenestrated retinal blood vessels indicated a disruption of the blood-retinal barrier, leading to albumin leak. The fenestrations were linked to contacts with the retinal pigment epithelium (RPE). In the central areas with more advanced RD, the density of choroidal capillaries was diminished. Within the large patches of compromised RPE, the choroid acquired blood-retinal barrier properties. Finally, the close proximity of choroid and retinal vasculature with the modified RPE and the remaining inner retina led to atypical perfusion through the fused choroidal and retinal vasculature, also known as chorioretinal anastomoses.
Assessment of retinal vasculature in the advanced stages of RD shows that structural degradation is preceded by the functional changes. The dynamic interaction within the unique vascular circulations of the retina leads to the emergence of atypical barrier properties and perfusion in RD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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