NDLI: Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shosha, E. Narayanan, S. P. Caldwell, R. B. Xing, J. Xu, Z. Caldwell, R. W. Patel, C. Lucas, R.
Description	Author Affiliation: Patel C ( Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA); Xu Z ( Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA); Shosha E ( Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA); Xing J ( Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA); Lucas R ( Vascular Biology Center, Augusta University, Augusta, GA 30912, USA); Caldwell RW ( Department of Pharmacology & Toxicology, Augusta University, Augusta, GA 30912, USA. Electronic address: wcaldwel@augusta.edu.); Caldwell RB ( Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA); Narayanan SP ( Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA)
Abstract	Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. New-born C57BL6/J mice were exposed to hyperoxia (70% O $_{2}$ ) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia.
ISSN	00063002
Journal	Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Issue Number	9
Volume Number	1862
Language	English
Publisher	Elsevier
Publisher Date	2016-09-01
Publisher Place	Netherlands
Access Restriction	Open
Subject Keyword	Biochemistry
Content Type	Text
Resource Type	Article

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