Small Molecule Cyclin-Dependent Kinase Inhibitors Protect Against Neuronal Cell Death in the Ischemic-Reperfused Rat Retina

Abstract Purpose: Recently, cell cycle reentry has been reported in the experimental brain ischemia model and Alzheimer's disease brain. Cyclin-dependent kinases (CDKs) are known to be key molecules that regulate the cell cycle. The aims of the present study were to determine the change in expression of the proteins involved in regulation of G1 phase, and to test the effect of small molecule CDK inhibitors on neuronal injury in the ischemic-reperfused rat retina. Methods: Male Sprague-Dawley rats were anesthetized and subjected to 60 min of retinal ischemia by raising intraocular pressure to 130 mmHg. One day after this procedure, the retinal tissues were homogenized and immunoblot analyses were done to check the expression levels of cell cycle regulatory proteins. Additional groups of rats received 3 mg/kg roscovitine, a CDK inhibitor, and 1 mg/kg CDK4 inhibitor intravenously (i.v.) 15 min before ischemia and underwent 60 min of ischemia. On the 7th day of the retinal ischemia-reperfusion, eyes were subj...