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Sara K. Akeel, Syliva Megyerdi, Saif Ahmad, Babak Baban, Vijay P. Sarthy, Mohamed Al-Shabrawey; Up-regulation of Bone Morphogenetic Protein-2 in Retina of Patients with Diabetic Retinopathy and Mouse Model of Experimental Diabetes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5976.
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Bone morphogenetic proteins (BMP) are extracellular proteins which belong to the transforming growth factor-β superfamily. In addition to their ability to contribute to the bone development, induction and repair, they also are involved in embryonic vascular development. BMP-2 is one of 20 BMPs that have been identified to date. It has been shown to promote angiogenesis and implicated in endothelial cell dysfunction. The purpose of this study was to test whether BMP-2 plays any role in the diabetic retinopathy (DR).
Experimental diabetes was induced in 6-8 weeks mice by streptozotocin injection (55 mg/kg). Immunohistochemistry, Immunoflurosecnce and Western blotting were used to assess the expression of BMP-2 in the retina of normal and diabetic mice and human retinas. Effect of BMP-2 (10 ng/ml) on VEGF production in cultured rat Muller cells (rMC1) was tested by ELISA.
There was marked increase in BMP-2 immunoreactivity in retinal vasculature of diabetic mice and human subjects with DR compared to the control. Diabetes increased total BMP-2 protein level in mouse retina. Furthermore, BMP-2 induces VEGF expression in rMC compared to the control (229+29 vs 97+29 pg/ml, P<0.05).
BMP-2 may have a major role in the pathogenesis of vascular dysfunction during diabetic retinopathy via up-regulating VEGF expression.
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