Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Research Article Ophthalmology Vascular biology

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

  • Text
  • PDF
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

×

Figure 1

Combinatorial approach for assessment of the vascular network and blood-retina barrier in living and fixed retinal tissue.

Options: View larger image (or click on image) Download as PowerPoint
Combinatorial approach for assessment of the vascular network and blood-...
(A) A dual nature of blood supply in the retina. Photoreceptors and retinal pigment epithelium (RPE) separate the outer and inner blood-retina barriers (BRBs). (B) BRB assessment protocol. (C) Identification of retinal poles in the eyecup preparation. The nasal-temporal axis is aligned with light choroidal marks (arrows); the dorsal pole corresponds to the white spot of the optic nerve head (arrowhead). (D) Hierarchy of retinal blood vessels. a, artery; v, vein. Numbers indicate branch order. (E–G) Quadruple-labeled confocal sections of the deep vascular layer in WT (E) and rd10 mice at P200 (F and G). A structural marker, isolectin, revealed a net of blood vessels in WT and rd10 retinas (green). In WT retina, all vessels were perfused by Evans Blue (white). In rd10 retina, only a fraction of capillaries was functional (F, arrow). Tortuous blood vessels in rd10 retina were leaky (G, arrowheads). In the fixed tissue, albumin (blue) reproduced Evans Blue pattern. Pericytes, labeled for neuron-glia antigen 2 (NG2), concentrated on perfusable blood vessels (magenta; bridging pericytes are marked by asterisks). In merged images, images were aligned by warp procedure to compensate for fixation-related distortion. (H and I) Isolectin (green) labels basement membrane around pericytes (magenta) and endothelial cells (blue); a bridging pericyte is shown (arrows). Degenerating retinal blood vessels in rd10 retina form empty vascular sleeves without endothelial cells or pericytes (I, arrowheads). Scale bars: 250 μm (C), 50 μm (D–I). SMA, smooth muscle actin; CD31, cluster of differentiation 31.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts