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R. Srinivasan, S. Rangasamy, J. Maestas, P. McGuire, A. Das; Angiopoietin- 2 Plays an Important Role in the Alteration of the Blood- Retinal- Barrier. Invest. Ophthalmol. Vis. Sci. 2009;50(13):37.
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Diabetic retinopathy is characterized by alteration of the blood-retinal-barrier and the development of retinal edema, and later by retinal angiogenesis. Our earlier studies have shown that angiopoietin-2 (Ang-2) is a factor that plays an important role in the pathogenesis of ocular angiogenesis. In this study we have examined the role of Ang-2 in mediating changes in endothelial barrier function both in vivo and in isolated retinal endothelial cells in culture.
Adult Sprague-Dawley rats received an intraocular injection of Ang-2 and retinal vascular permeability was assessed by the Evans blue dye technique. Human retinal endothelial cells (HRECs) were grown to confluence on transwell filters and the integrity of the monolayer was determined using FITC-Dextran following treatment with increasing concentrations of Ang-2.. Alteration of VE-Cadherin in response to Ang-2 stimulation was assessed by measuring the extent of tyrosine phosphorylation by western blot.
The intraocular injection of Ang-2 resulted in a significant increase in retinal vascular permeability when compared to rats injected with PBS alone. Ang-2 increased monolayer permeability in HRECs in a concentration dependent manner. Ang-2 was also found to produce a significant increase in VE-Cadherin phosphorylation in HREC.
We have previously shown increased expression of Ang-2 in animals during the early stages of diabetic retinopathy. In this study Ang-2 was found to increase endothelial vascular permeability both in vivo and in vitro possibly through alteration of VE-cadherin phosphorylation. Thus a better understanding of Ang-2 function in the retina may help in the development of novel therapies for diabetic macular edema.
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