Modulation of Radiation Injury Response in Retinal Endothelial Cells by Quinic Acid Derivative KZ-41 Involves p38 MAPK

• DOI: 10.1371/journal.pone.0100210
• Publication Date: 2014-06-23T20:23:26Z
• Authors: Jordan J. Toutoun...; Jena J. Steinle; Patrudu S. Makena; Christopher M. Wa...; Matthew W. Wilson; Barrett G. Haik; Duane D. Miller; Charles R. Yates
• Keywords: Paxillin; Quinic acid

Radiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC) death, and subsequent hypoxia. Resultant ischemia leads visual loss compensatory neovascularization (RNV). Using human RECs, we demonstrated that radiation induced leukocyte adhesion through mechanisms involving p38MAPK, p53, ICAM-1 activation. Additional phenotypic changes included p38MAPK-dependent tyrosine phosphorylation of focal scaffolding protein, paxillin (Tyr118). The quinic acid derivative KZ-41 lessened paxillin-dependent proliferation via inhibition p38MAPK-p53-ICAM-1 signaling. murine oxygen-induced retinopathy (OIR) model, examined effect on pathologic RNV. Daily ocular application a KZ-41-loaded nanoemulsion significantly reduced both avascular neovascular areas in harvested flat mounts when compared contralateral eye receiving vehicle alone. Our data highlight potential benefit reducing provoked by genotoxic insults. Further research into how derivatives target mitigate inflammation is needed fully appreciate their therapeutic for treatment inflammatory vasculopathies.