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S. Rangasamy, R. Srinivasan, J. Maestas, P. McGuire, A. Das; Alterations of Angiopoietin 1 and 2 Expression in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):19. doi: https://doi.org/.
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One of the hallmarks of diabetic retinopathy is the alteration of the blood-retinal barrier resulting in macular edema. Although the VEGF has been identified as an important mediator of this process, there are other molecules which may also play a role. To study the role of angiopoietins in alteration of the blood-retinal-barrier, we examined the expression pattern of angiopoietins in an animal model of diabetic retinopathy, as well as in human retinal endothelial cells (HRECs) treated with high glucose and high glucose flux.
Diabetes was induced in Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin. HRECs were grown to confluence, and treated with high glucose (30.5 mM) for 72 hours and glucose flux (alternate cycles of 5.5mM and 30.5 mM) for a total of 72 hours. RNA was extracted from the rat retina and HRECs, and angiopoietins 1 and 2 (Ang-1 & Ang-2) levels were analyzed by quantitative RT-PCR and western blot analysis.
There is a significant increase in Ang -2 mRNA levels in retinal tissues of rats with 5 and 8 week duration of diabetes. HRECs treated with high glucose and glucose flux conditions showed a significant elevation in the levels of both Ang-1 and Ang-2. The increased levels of Ang-2 protein were also confirmed by western blot analysis in cells treated with high glucose. Interestingly, the ratio of Ang-2/Ang-1 was elevated in both HRECs and in the retinas of diabetic rats.
Hyperglycemia induces the expression of both Ang-1 and Ang-2 in diabetic rat retina and isolated retinal endothelial cells. An understanding of the role of angiopoietins during the early stages of diabetic retinopathy may help us to elucidate the molecular mechanisms of blood-retinal-barrier alteration, and possibly lead to the development of novel therapeutic targets for this disease.
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