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Y. Jiang, T. S. Kern, J. J. Steinle; Beta-Adrenergic Receptor Eye Drop Therapy Prevents Retinal Changes Associated with Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4807.
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To evaluate the effectiveness of beta-adrenergic receptor agonist as eye drop therapy to prevent the acute and chronic changes commonly associated with diabetic retinopathy.
Male rats were made diabetic by a single injection of 60mg/kg streptozotocin (STZ) dissolved in citrate buffer. Diabetic animals were characterized as having a glucose level >200mg/dl within 3 days of STZ injection. Three groups of animals were used for this work: control animals that received citrate buffer only; rats that received only the STZ injection; and animals that were diabetic and received isoproterenol eye drops for 2months (acute) or 8months (chronic). The eye drop application consisted of isoproterenol, a non-specific beta-adrenergic receptor agonist, given once every 24 hours at a concentration of 50mM started immediately after the initial glucose test. Each month, rats from all groups underwent electroretinogram (ERG) analyses. At 2 months, rats from each group were sacrificed and analyzed for retinal thickness and cell numbers in the ganglion cell layer. At 8 months, analyses of pericyte ghosts and degenerate capillaries were done to evaluate the effectiveness of the therapy for prevention of diabetic-like changes.
Diabetes resulted in a significant decrease in the amplitude of the B-wave and oscillatory potentials in the ERG at all time points. These decreases in amplitudes were prevented by daily application of the isoproterenol eye drops. At 2 months, the retinal thickness was significantly reduced in the diabetic rats, which did not occur in the diabetic plus treatment group. The isoproterenol eye drops also prevented the decrease in cell numbers in the retinal ganglion cell layer that was noted in the diabetic rats at 2months of diabetes. In the chronic studies, the eye drop therapy was able to prevent the formation of degenerative capillaries in the retina.
Eye drop therapy of beta-adrenergic receptor agonists was effective in decreasing the loss of cells in the ganglion cell layer and formation of degenerate capillaries, which commonly occur in the diabetic rat retina. The isoproterenol eye drops also prevented the diabetes-induced decrease in ERG amplitudes over the entire experimental time frame. These studies should lay the groundwork for further studies in larger animal models of beta-adrenergic receptor agonists for prevention of diabetic-like retinal changes.
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