Abstract
Purpose: :
To determine whether Compound 49b, a novel β-adrenergic receptor agonist, increases IGFBP3 levels to inhibit apoptosis in the diabetic retina.
Methods: :
Male rats were made diabetic with a single injection of streptozotocin (60mg/kg). Three groups of rats were used: control, diabetic, and diabetic+Compound 49b treated. Compound 49b eye drops (1 mM) were administered daily. After 8 months of treatment, retinal protein levels of IGFBP-3, Bad, Fas, Fas ligand, and Bcl-xl, and cleaved caspase 3 levels were measured by Western blot or ELISA.
Results: :
Compound 49b eye drops increased IGFBP3 levels (P<0.05 vs. untreated diabetic). Concurrent with the increase in IGFBP3, Compound 49b treatment significantly decreased levels of key pro-apoptotic markers Bad, Fas, Fas ligand, and cleaved caspase 3 (P<0.05 vs untreated diabetic retina).
Conclusions: :
A novel β-adrenergic receptor agonist, Compound 49b, can significantly increase IGFBP3 levels in the diabetic retina, while decreasing key pro-apoptotic markers. This is the first demonstration of regulation of IGFBP3 by β-adrenergic receptor agonists, as well as a potential anti-apoptotic mechanism for IGFBP3. Future studies will investigate the mechanism by which native IGFBP3 may inhibit retinal endothelial cell death.
Keywords: apoptosis/cell death • diabetic retinopathy • signal transduction