Purchase this article with an account.
Y.-Z. Le, J. Wang, H. Xu; Pathophysiology of Outer Blood-Retina Barrier Breakdown. Invest. Ophthalmol. Vis. Sci. 2010;51(13):498.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Although outer blood-retina (BRB) barrier is responsible for approximately 80% of blood circulation in the retina, the pathophysiology of outer BRB is not well-studied. To determine the significance of outer BRB breakdown in retinal vascular diseases, we investigated outer BRB-specific leakage in mice with altered RPE barrier in ischemia and uveitis models.
Mice with altered outer BRB were generated by disrupting vascular endothelial growth factor (VEGF) or VEGF-receptor 2 (R2) in the RPE. Ischemia was induced with an oxygen-induced retinopathy (OIR) and uveitis was generated with endotoxin-induced uveitis (EIU). The alteration of outer BRB was assessed by measuring tight-junction protein occludin in the RPE with Western blot and immunohistochemistry. The outer BRB-specific leakage of macromolecules were visualized and measured by a fluorescent microscopic assay.
For the first time, we were able to visualize and measure outer BRB-specific leakage in ischemic mice. Outer BRB-specific breakpoints and macromolecule leakage were significantly reduced in the OIR-treated conditional VEGF or VEGF-R2 KO mice. EIU-treated conditional VEGF KO mice demonstrated a significant reduction in the size of retinal detachments and the amount of outer BRB-specific leakage. These pathological changes were associated with an attenuation of occludin depletion in the conditional VEGF or VEGF-R2 KO mice.
Our newly established fluorescent microscopic assay permits the visualization and measurement of outer BRB breakdown in ischemic mice for the first time. Our results suggest that the breakdown of outer BRB contributes significantly to overall blood-content leakage under ischemic condition and exudative retinal detachment under uveitic condition, through an autocrine VEGF signaling mechanism. Therefore, our study may have significant implications to the mechanism, diagnosis, and therapeutics of retinopathy of prematurity, uveitis, and macular edema.
This PDF is available to Subscribers Only