Cdk5-mediated Drp1 phosphorylation drives mitochondrial defects and neuronal apoptosis in radiation-induced optic neuropathy.
MixedRadiationBALB/cMaleIntraperitoneal (in vivo); culture medium (in vitro)In vivo: mdivi-1 3 mg/kg and roscovitine 3.5 mg/kg intraper…First dose 6 h before irradiation; in vitro drug added 2 h before irradiation
Model: Radiation-induced optic neuropathy produced by head-only X-ray irradiation (10 Gy selected after dose finding at 0, 8, 10 and 12 Gy, dose rate 600 rad/min); in vitro 6 Gy X-ray irradiation of R28 cells
Head irradiation increased phospho-Drp1 (Ser616), Fis1 and Cdk5, raised reactive oxygen species, fragmented mitochondria, reduced retinal ganglion cell numbers and outer nuclear layer thickness, and delayed and attenuated visual-evoked potential P1 and P2 waves. Both mdivi-1 and roscovitine suppres…
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