کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4011702 1261159 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Application of isoproterenol inhibits diabetic-like changes in the rat retina
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
Application of isoproterenol inhibits diabetic-like changes in the rat retina
چکیده انگلیسی

Diabetic retinopathy is the leading cause of blindness to working-age adults. We have recently shown that surgical removal or genetic manipulations to eliminate sympathetic neurotransmission produces many of the retinal changes similar to rodent diabetic retinopathy with normal glucose levels. We hypothesized that application of a beta-adrenergic receptor agonist, isoproterenol, could reach the retina to elicit normal cellular signaling and inhibit the functional and morphological markers of early stage diabetic retinopathy in the rat. Rats were made diabetic by injection of 60 mg/kg streptozotocin. Within 3 days of diabetes-induction, rats were placed into 1 of 3 groups (control, diabetes, or diabetic + isoproterenol). Dose and time course studies were done for isoproterenol using a PKA ELISA and CREB analyses. Once the optimal dose and time course were established, electrical activity of the retina was analyzed by electroretinogram each month for the 8-month study. Western blotting was done for insulin receptor signaling and Akt and ELISA analyses for TNFα concentration and cleavage of caspase 3 at 2- and 8-months of diabetes. Diabetes-induced degeneration of neural cells and retinal thickness were assessed at 2 months, while degenerate capillaries were quantitated at 8 months of treatment. Daily application of 50 mM isoproterenol was effective in inhibiting the diabetes-induced loss of a- and b-wave and oscillatory potential amplitudes in the electroretinogram. Isoproterenol blocked the increase in TNFα and apoptosis in the diabetic retina. The numbers of degenerate capillaries were also reduced in the treated + diabetes retina. These data strongly suggest that loss of beta-adrenergic receptor signaling may be a key factors in early stage diabetic retinopathy. Resolution of this loss of adrenergic receptor signaling can inhibit some of the hallmarks of diabetic retinopathy in the retina.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 91, Issue 2, August 2010, Pages 171–179
نویسندگان
, , , ,