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K. P. Williams, J. Pagadala, D. D. Miller, J. J. Steinle; Novel Beta Adrenergic Receptor Agonist in the Treatment of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5630.
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The goal of this study was to test whether a novel beta-adrenergic receptor agonist can reduce apoptosis and TNFα in vitro. This agent will also be used topically for chronic studies of diabetic retinopathy.
Retinal endothelial cells and Müller cells were cultured in high glucose (25mM) media. Cells were treated with various novel beta-adrenergic receptor agonists at specific dosages and time points. Cells receiving no treatment served as controls. Caspase-3 ELISA and TNF-α ELISAs were performed to evaluate apoptosis and inflammatory markers. Two-month diabetic rats were treated for 4 days with compound 49b, followed by PKA ELISA and CREB Western blotting to optimize the dose of 49b.
Compound 49b significantly reduced caspase-3 and TNF-α levels in both cell types. Caspase-3 and TNF-α levels were significantly reduced at 50nM in cultured cells, a dose lower than that of a non-specific beta-adrenergic agonist, isoproterenol. PKA levels were significantly increased in diabetic rats treated with 49b at a dose of 10mM.
These results indicate that a novel beta-adrenergic receptor agonist is able to reduce inflammation and cell death, common features of non-proliferative diabetic retinopathy. The topical application of the novel compound is currently being tested in vivo in chronic diabetes at 10mM. We will assess diabetic-like changes at 2 and 8-months following treatment.
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