Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy
Vähätupa, M., Prince, S., Vataja, S., Mertimo, T., Kataja, M., Kinnunen, K., Marjomäki, V., Uusitalo, H., Komatsu, M., Järvinen, T. A., & Uusitalo–Järvinen, H. (2016). Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy. Investigative Ophthalmology and Visual Science, 57(11), 4898-4909. https://doi.org/10.1167/iovs.16-19212
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Investigative Ophthalmology and Visual ScienceAuthors
Date
2016Copyright
© the Authors, 2016. This is an open access article licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
PURPOSE. The role of R-Ras in retinal angiogenesis and vascular permeability was evaluated in
an oxygen-induced retinopathy (OIR) model using R-Ras knockout (KO) mice and in human
diabetic neovascular membranes.
METHODS. Mice deficient for R-Ras and their wild-type (WT) littermates were subjected to 75%
oxygen from postnatal day 7 (P7) to P12 and then returned to room air. At P17 retinal
vascularization was examined from whole mounts, and retinal vascular permeability was
studied using Miles assay. Real-time RT-PCR, Western blotting, and immunohistochemistry
were used to assess the expression of R-Ras in retina during development or in the OIR
model. The degree of pericyte coverage and vascular endothelial (VE)-cadherin expression on
WT and R-Ras KO retinal blood vessels was quantified using confocal microscopy. The
correlation of R-Ras with vascular endothelial growth factor receptor 2 (VEGFR2) and human
serum albumin on human proliferative diabetic retinopathy membranes was assessed using
immunohistochemistry.
RESULTS. In retina, R-Ras expression was mostly restricted to the vasculature. Retinal vessels in
the R-Ras KO mice were significantly more permeable than WT controls in the OIR model. A
significant reduction in the direct physical contact between pericytes and blood vessel
endothelium as well as reduced VE-cadherin immunostaining was found in R-Ras–deficient
mice. In human proliferative diabetic retinopathy neovascular membranes, R-Ras expression
negatively correlated with increased vascular leakage and expression of VEGFR2, a marker of
blood vessel immaturity.
CONCLUSIONS. Our results suggest that R-Ras has a role in controlling retinal vessel maturation
and stabilization in ischemic retinopathy and provides a potential target for pharmacologic
manipulation to treat diabetic retinopathy.
...


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Except where otherwise noted, this item's license is described as © the Authors, 2016. This is an open access article licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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