dc.contributor.author | Vähätupa, Maria | |
dc.contributor.author | Prince, Stuart | |
dc.contributor.author | Vataja, Suvi | |
dc.contributor.author | Mertimo, Teija | |
dc.contributor.author | Kataja, Marko | |
dc.contributor.author | Kinnunen, Kati | |
dc.contributor.author | Marjomäki, Varpu | |
dc.contributor.author | Uusitalo, Hannu | |
dc.contributor.author | Komatsu, Masanobu | |
dc.contributor.author | Järvinen, Tero A.H. | |
dc.contributor.author | Uusitalo–Järvinen, Hannele | |
dc.date.accessioned | 2016-10-13T06:57:46Z | |
dc.date.available | 2016-10-13T06:57:46Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | 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. <i>Investigative Ophthalmology and Visual Science</i>, <i>57</i>(11), 4898-4909. <a href="https://doi.org/10.1167/iovs.16-19212" target="_blank">https://doi.org/10.1167/iovs.16-19212</a> | |
dc.identifier.other | CONVID_26262980 | |
dc.identifier.other | TUTKAID_71437 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/51616 | |
dc.description.abstract | 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. | |
dc.language.iso | eng | |
dc.publisher | Association for Research in Vision and Ophthalmology | |
dc.relation.ispartofseries | Investigative Ophthalmology and Visual Science | |
dc.subject.other | neovascularization | |
dc.subject.other | retinal ischemia | |
dc.title | Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy | |
dc.type | article | |
dc.identifier.urn | URN:NBN:fi:jyu-201610114327 | |
dc.contributor.laitos | Bio- ja ympäristötieteiden laitos | fi |
dc.contributor.laitos | Department of Biological and Environmental Science | en |
dc.contributor.oppiaine | Solu- ja molekyylibiologia | fi |
dc.contributor.oppiaine | Nanoscience Center | fi |
dc.contributor.oppiaine | Cell and Molecular Biology | en |
dc.contributor.oppiaine | Nanoscience Center | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
dc.date.updated | 2016-10-11T09:15:03Z | |
dc.type.coar | http://purl.org/coar/resource_type/c_2df8fbb1 | |
dc.description.reviewstatus | peerReviewed | |
dc.format.pagerange | 4898-4909 | |
dc.relation.issn | 0146-0404 | |
dc.relation.numberinseries | 11 | |
dc.relation.volume | 57 | |
dc.type.version | publishedVersion | |
dc.rights.copyright | © the Authors, 2016. This is an open access article licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | |
dc.rights.accesslevel | openAccess | fi |
dc.subject.yso | verkkokalvo | |
dc.subject.yso | diabeettinen retinopatia | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p21732 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p38465 | |
dc.rights.url | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.relation.doi | 10.1167/iovs.16-19212 | |
dc.type.okm | A1 | |