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N. Sheibani, S. Wang, S. Park, E. A. Scheef, C. M. Sorenson; Lack of Doxycycline Angioinhibitory Activity in Retinal and Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):45.
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Doxycycline-mediated gene regulation has been extensively utilized for evaluation of various gene functions in a tissue specific manner. The purpose of the current study was to determine the effect of doxycycline administration on postnatal retinal vascular development and neovascularization, as well as choroidal neovascularization (CNV) in vivo and retinal endothelial cell (EC) function in vitro.
The potential antiangiogenic activity of doxycycline was evaluated during postnatal development of mouse retinal vasculature using established immunohistological methods. The impact of doxycycline on retinal neovascularization was assessed during oxygen-induced ischemic retinopathy (OIR). We also evaluated the activity of doxycycline in the mouse laser-induced CNV model and ex vivo aortic sprouting assay. In addition, we determined the effects of doxycycline on mouse retinal EC function in culture using various cell biological and biochemical methods.
We show that administration of doxycycline minimally impacted normal postnatal retinal vascularization and retinal neovascularization during OIR. We observed no significant effect on CNV or aortic sprouting following administration of doxycycline. Doxycycline also had minimal effect on retinal EC proliferation, apoptosis, capillary morphogenesis, and permeability. These observations were consistent with minimal effect of doxycycline on expression of cell adhesion molecules PECAM-1 and VE-cadherin on the surface of retinal EC and their junctional localization.
The impact of doxycycline administration on retinal vascular development and neovascularization in vivo, and retinal EC function in vitro, was minimal. Doxycycline also showed no significant effect on CNV or aortic sprouting.
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