Inhibition of roscovitine on the activity of Cdk5/p25 and phosphorylation of tau in retina of RCS rats after intravitreal injection

Background Study determined that retinitis pigmentosa has a similar pathogenesis mechanism to Alzheimer disease, and activity of cyclin-dependent kinase 5(Cdk5) and its activators participates in the degeneration of central nervous system.Roscovitine, an inhibitor of Cdk5, can suppress activity of Cdk5/p25 pathway and therefore inhibit cell apoptosis.However, the influence of roscovitine on retinitis pigmentosa(RP) is unclear. Objective This study was to investigate the expressions of p35, p25 and tau in the retinas of RCS rats. Methods Roscovitine of 4 μl was intravitreally injected in the right eyes of 12 SPF 17-day-old RCS rats, and the fellow eyes were not intervened as the control eyes.The rats were sacrificed on eighth day (postnatal 25 days) and eighteenth day (postnatal 35 days), and whole retinas were isolated to evaluate the relative expressions of Cdk5, p35, p25 and tau phosphorylation by Western blot, and the activity of Cdk5/p25 was analyzed by quantitative colorimetric assay.The results were compared between the right eyes and fellow eyes by paired t test.The use and care of the rats complied with Ethic Statement of Experimental Animal of Ningxia Medical University. Results In the eighth and eighteenth day after injection, the relative expression values (A values) of p35 in rat retinas were 1.186±0.019 and 1.069±0.019 in the injected eyes, showing significant decreases in comparison with 1.364±0.016 and 1.214±0.008 of the fellow eyes (t=-6.294, -6.477, both at P 0.05).The activities of Cdk5/p25 were (0.003 83±0.000 14)mol/(s·mg) and (0.002 01±0.000 11)mol/(s·mg) in the injected eyes, with significant decreases in comparison with the (0.005 47±0.000 27)mol/(s·mg) and (0.003 35±0.000 15) mol/(s·mg) of the fellow eyes (t=-9.152, P=0.000;t=-9.248, P=0.000), and the tau phosphorylation levels followed the same pattern in the eighth and eighteenth day after injection (t=-9.854, -6.744, both at P<0.05). Conclusions Intravitreal injection of roscovitine can inhibit the activity of Cdk5/p25 and tau phosphorylation level in retinas of RCS rats to certain extend. Key words: Cdk5/p25; Inhibitor; Roscovitine; Apoptosis; Rat, RCS; Retinal degeneration/genetics