Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK.
Radiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC) death, and subsequent hypoxia. Resultant ischemia leads to visual loss and compensatory retinal neovascularization (RNV). Using human RECs, we demonstrated that radiation induced leukocyte adhesion through me...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4067294?pdf=render |
| _version_ | 1818859151734865920 |
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| author | Jordan J Toutounchian Jena J Steinle Patrudu S Makena Christopher M Waters Matthew W Wilson Barrett G Haik Duane D Miller Charles R Yates |
| author_facet | Jordan J Toutounchian Jena J Steinle Patrudu S Makena Christopher M Waters Matthew W Wilson Barrett G Haik Duane D Miller Charles R Yates |
| author_sort | Jordan J Toutounchian |
| collection | DOAJ |
| description | Radiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC) death, and subsequent hypoxia. Resultant ischemia leads to visual loss and compensatory retinal neovascularization (RNV). Using human RECs, we demonstrated that radiation induced leukocyte adhesion through mechanisms involving p38MAPK, p53, and ICAM-1 activation. Additional phenotypic changes included p38MAPK-dependent tyrosine phosphorylation of the focal adhesion scaffolding protein, paxillin (Tyr118). The quinic acid derivative KZ-41 lessened leukocyte adhesion and paxillin-dependent proliferation via inhibition of p38MAPK-p53-ICAM-1 signaling. Using the murine oxygen-induced retinopathy (OIR) model, we examined the effect of KZ-41 on pathologic RNV. Daily ocular application of a KZ-41-loaded nanoemulsion significantly reduced both the avascular and neovascular areas in harvested retinal flat mounts when compared to the contralateral eye receiving vehicle alone. Our data highlight the potential benefit of KZ-41 in reducing both the retinal ischemia and neovascularization provoked by genotoxic insults. Further research into how quinic acid derivatives target and mitigate inflammation is needed to fully appreciate their therapeutic potential for the treatment of inflammatory retinal vasculopathies. |
| first_indexed | 2024-12-19T09:07:38Z |
| format | Article |
| id | doaj.art-2fa3b981e4d44911a6c66d716e34c0e9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T09:07:38Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2fa3b981e4d44911a6c66d716e34c0e92022-12-21T20:28:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e10021010.1371/journal.pone.0100210Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK.Jordan J ToutounchianJena J SteinlePatrudu S MakenaChristopher M WatersMatthew W WilsonBarrett G HaikDuane D MillerCharles R YatesRadiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC) death, and subsequent hypoxia. Resultant ischemia leads to visual loss and compensatory retinal neovascularization (RNV). Using human RECs, we demonstrated that radiation induced leukocyte adhesion through mechanisms involving p38MAPK, p53, and ICAM-1 activation. Additional phenotypic changes included p38MAPK-dependent tyrosine phosphorylation of the focal adhesion scaffolding protein, paxillin (Tyr118). The quinic acid derivative KZ-41 lessened leukocyte adhesion and paxillin-dependent proliferation via inhibition of p38MAPK-p53-ICAM-1 signaling. Using the murine oxygen-induced retinopathy (OIR) model, we examined the effect of KZ-41 on pathologic RNV. Daily ocular application of a KZ-41-loaded nanoemulsion significantly reduced both the avascular and neovascular areas in harvested retinal flat mounts when compared to the contralateral eye receiving vehicle alone. Our data highlight the potential benefit of KZ-41 in reducing both the retinal ischemia and neovascularization provoked by genotoxic insults. Further research into how quinic acid derivatives target and mitigate inflammation is needed to fully appreciate their therapeutic potential for the treatment of inflammatory retinal vasculopathies.http://europepmc.org/articles/PMC4067294?pdf=render |
| spellingShingle | Jordan J Toutounchian Jena J Steinle Patrudu S Makena Christopher M Waters Matthew W Wilson Barrett G Haik Duane D Miller Charles R Yates Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. PLoS ONE |
| title | Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. |
| title_full | Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. |
| title_fullStr | Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. |
| title_full_unstemmed | Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. |
| title_short | Modulation of radiation injury response in retinal endothelial cells by quinic acid derivative KZ-41 involves p38 MAPK. |
| title_sort | modulation of radiation injury response in retinal endothelial cells by quinic acid derivative kz 41 involves p38 mapk |
| url | http://europepmc.org/articles/PMC4067294?pdf=render |
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