Relationship between cyclin dependent kinase 5 and apoptosis in the pathogenesis of retinitis pigmentosa in Royal College of Surgeon rats

Abstract

Objective To observe the expression of cyclin dependent kinase 5 (Cdk5) and p25 in the pathogenesis of retinitis pigmentosa (RP) in Royal College of Surgeon (RCS) rats and its relationships with apoptosis.To explore the mechanism of Cdk5 and p25 induced photoreceptor apoptosis in the pathogenesis of RP.Methods Retinas of RCS and RCS-rdy+ rats were obtained at the ages of postnatal day 17,25,35,60.The retinal structure and thickness of outer nuclear layer were measured by optical microscopy.The expression of Cdk5,p25,cleave-caspase 3 in the retina was evaluated by immunohistochemistry.The protein expression of cleave-caspase 3 in the retina was determined by Western blot.The apoptosis of retinal cells was examined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL).The mean absorbance value of apoptotic cells was analyzed by SPSS 17.0 software.Results The retinal thickness of the RCS rats was significantly reduced in comparison to the RCS-rdy+ rats as the postnatal days progressed,particularly in the layer of rods and cones and the outer nuclear layer.The expression level of Cdk5,p25,cleave-caspase 3 of RCS rats increased from postnatal 17 days to postnatal 35 days,while decreased on postnatal 60 days; but there was no obvious change of above indexes in RCS-rdy+ rats.The protein expression of cleave-caspase 3 in the RCS rats was significantly increased with progression of postnatal days to postnatal 35; but there was no obvious similar change in RCS-rdy-rats.The results of TUNEL showed that the apoptotic cells significantly increased in the outer nuclear layer of RCS rats from postnatal 17 days to postnatal 35 days,while decreased on postnatal 60 days; but there was no obvious change of above index in RCS-rdy+ rats.This study showed that there were significant correlations between the following variables..Cdk5 expression and p25 expression,Cdk5 expression and cleave-caspase 3 expression,Cdk5 expression and apoptotic cells,p25 expression and cleave-caspase 3 expression,p25 expression and apoptotic cells,cleave-caspase 3 expression and apoptotic cells.The partial correlation coefficients were 0.949,0.808,0.959,0.887,0.979,0.852,respectively and the P value was 0.000.Conclusions The apoptotic ceils significantly increases and the expression level of Cdk5,p25,cleavecaspase 3 of RCS rats increases from postnatal 17 days to postnatal 35 days.The tendency of apoptotic cells to increase is consistent with the change of Cdk5,p25,cleave-caspase 3 expression.The apoptosis of photoreceptor cells is related to increasing expression of Cdk5 and p25 in RCS rats.Cdk5 may be involved in the development of RP in RCS rats. Key words: Retinitis pigmentosa/pathophysiology; Cyclin-dependent kinase 5; Apoptosis; Animal experimentation