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Blood-retina barrier failure and vision loss in neuron-specific degeneration
Elena Ivanova, … , Glen T. Prusky, Botir T. Sagdullaev
Elena Ivanova, … , Glen T. Prusky, Botir T. Sagdullaev
Published March 19, 2019
Citation Information: JCI Insight. 2019;4(8):e126747. https://doi.org/10.1172/jci.insight.126747.
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Research Article Ophthalmology Vascular biology

Blood-retina barrier failure and vision loss in neuron-specific degeneration

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Abstract

Changes in neuronal activity alter blood flow to match energy demand with the supply of oxygen and nutrients. This functional hyperemia is maintained by interactions among neurons, vascular cells, and glia. However, how changing neuronal activity prevalent at the onset of neurodegenerative disease affects neurovascular elements is unclear. Here, in mice with photoreceptor degeneration, a model of neuron-specific dysfunction, we combined the assessment of visual function, neurovascular unit structure, and blood-retina barrier permeability. We found that the rod loss paralleled remodeling of the neurovascular unit, comprising photoreceptors, retinal pigment epithelium, and Muller glia. When substantial visual function was still present, blood flow became disrupted and the blood-retina barrier began to fail, facilitating cone loss and vision decline. Thus, in contrast to the established view, the vascular deficit in neuronal degeneration is not a late consequence of neuronal dysfunction but is present early in the course of disease. These findings further establish the importance of vascular deficit and blood-retina barrier function in neuron-specific loss and highlight it as a target for early therapeutic intervention.

Authors

Elena Ivanova, Nazia M. Alam, Glen T. Prusky, Botir T. Sagdullaev

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Figure 5

Cone loss and the presence of vascular leak in the advanced stages of retinal degeneration.

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Cone loss and the presence of vascular leak in the advanced stages of re...
(A) In rd10 mice, cones (arrestin, green) were absent in the areas with vascular leak (albumin, blue) coming from fenestrated vasculature (plasmalemma vesicle-associated protein [PLVAP], magenta, arrows). (B–D) Magnified areas from A. In WT, cones were evenly distributed through the retina; no albumin labeling was detected outside of the capillaries. In rd10 mice, regions with leak (D) corresponded to lower densities of cones. Most capillaries of the deep layer were degenerated in rd10 mice. (E) The majority of the surviving cones were found in the periphery, especially of the dorsal pole. (F) Mander’s indices show that areas with surviving cones and areas with blood-retina barrier leak do not overlap. (G) Leak was seen in patches, predominantly across central areas and around deep layer capillaries in the periphery. Scale bar: 1 mm (A); 50 μm (B–D). Data are represented as average ± SD (6 mice, each measurement). Two-tailed t test, *P < 0.05, **P < 0.01, ***P < 0.001.

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