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B. Anand-Apte, Q. Ebrahem, A. Cutler, J. Hollyfield, J. Folkman; Betacellulin Induces Increased Retinal Vascular Permeability in Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3297.
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Diabetic maculopathy, the leading cause of vision loss in patients with type 2 diabetes is characterized by hyper-permeability of retinal blood vessels with subsequent formation of macular edema and hard exudates. Epidemiological studies have suggested that glycemic control plays a major role in the development of vascular complications of diabetes. Current insulin therapies for control of glucose metabolism have not been successful in the prevention of long-term complications. It is critical to identify a downstream glycemic target that causes increased retinal vascular permeability and macular edema that could be targeted therapeutically without the additional risks associated with intensive treatment of the hyperglycemia.
Streptozocin-induced diabetic mice with hyperglycemia (blood sugar > 200mg/ml) were examined for increases in retinal vascular permeability and expression of betacellulin in the retina using an Evan's Blue leakage assay. The ability of intravitreally injected recombinant betacellulin to induce retinal vascular leakage was also evaluated by measuring the extravasation of intravascular Evan's Blue dye.
Diabetic mice show accentuated retinal vascular permeability and increased expression of betacellulin1 in the retina. Intravitreal injection of betacellulin induces retinal hemorrhage and increased vascular permeability in normoglycemic mice. Western blot analysis of retinas from control subjects and patients with diabetes with and without PDR demonstrate an increase in a 19kDa isoform of betacellulin in PDR retinas.
Regenerating beta cells in the diabetic pancreas may release excessive amounts of betacellulin and contribute to increased retinal vascular permeability and the pathogenesis of macular edema.1 Shing,y et al Science (1993), 259:1604-1607
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