Purchase this article with an account.
J. L. Bromberg-White, E. Boguslawski, N. S. Duesbery; MAPK Signaling Plays a Role in the Development and Progression of Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3348.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
In a previous study we showed that MAPK signaling plays a key role in retinal angiogenesis, and that inhibition of the MAPK pathways by anthrax lethal toxin (LeTx) can profoundly alter vascular morphogenesis (Bromberg-White et. al.  PLoS One, e6956). The goal of this study is to determine the role of MAPK signaling in the development and progression of retinal neovascularization, utilizing a mouse model of oxygen-induced retinopathy.
The pattern and cell-specificity of MAPK activation was analyzed during oxygen-induced retinopathy and subsequent development of neovascularization by immunoblotting and immunofluorescent imaging of retinal whole mounts. To assess the role of MAPK activation during oxygen-induced retinopathy, LeTx was injected intravitreally on return to a normoxic environment and subsequent effects on vascularization, vaso-obliteration, and neovascularzation were observed.
Western analysis revealed that MAPK activation preceded the development of neovascularization following oxygen-induced retinopathy. Furthermore, active MAPK was associated with a non-endothelial cell compartment, presumably inflammatory cells such as macrophages. Lethal toxin administration following oxygen-induced retinopathy resulted in a marked delay in the development of retinal neovascularization as well as a complete inhibition in the revascularization of vaso-obliterated regions of the retina.
These results suggest that MAPK signaling pathways are activated in response to hypoxic insult following oxygen-induced retinopathy, and that MAPK activation is associated with a non-endothelial cell compartment. Furthermore, inhibition of MAPK signaling by LeTx indicates that MAPK pathways play a crucial role in the development and progression of retinal neovascularization following oxygen-induced retinopathy.
This PDF is available to Subscribers Only