The Efficacy Of Idebenone For Retina Ischemia-reperfusion Injury

Background and ObjectiveRetina ischemia-reperfusion injury(RIRI)is the common pathophysiological process of many diseases that can lead to blindness.One of the main mechanisms may be oxidative stress-induced apoptosis of retinal ganglion cells(RGCs).Mitochondrion is the only organelle that contains genetic materials and has key regulational roles in cell survival and apoptosis.Mitochondrion disorder promotes the expression of apotosis-related proteins and actives endogenous apoptosis pathway.Coenzyme Q10 is an essential cofactor and potent antioxidant in the mitochondrial electron transport chain,playing significant protective roles in oxidative stress damages of neurodegenerative diseases.Idebenone is a mitochondrial function targeted clinical drug.It has similar quinone ring structure with coenzyme Q10 and better water solubility.It can be easily absorbed by the human body and is a very effective antioxidant and neuroprotective agent.It is reported to be protective in therophy for cerebral vascular diseases and inherited mitochondrial dysfunction disease.Materials and methodsRats were randomly divided into 3 group: Sham group,RIRI group and RIRI+ idebenone group.We use HE staining and immunohistochemistry to observe the retinal morphology and expression of caspase-3 at 12 h,24h,48 h and 72 h after RIRI operation.Western blot was used to evaluate the expression of Cytochrome C at 24 h after the reperfusion.Immunohistochemistry was also used to observe the number of THY1-1 positive RGCs.We use SPSS 21.0 to analyse data.All values were mean ± SD.P<0.05 means the difference was significant.ResultsHE staining: The retinal morphology and structure were normal in rats of Sham group.RIRI rats showed retinal edema,disordganized struction and less cells in ganglion cell layers than those in Sham group.Rats that received idebenone treatment exhibited better organized structure and sligher edema than rats in RIRI group.Expression of caspase-3: Rats in Sham group showed little expression of caspase 3 in immunohistochemistry.RIRI rats showed higher expression of caspase 3 than those in Sham group.The level of caspase-3 expression after Idebenone treatment was lower than that in RIRI group.After RIRI operation,the number of RGCs is higher than that in Sham group.After Idebenone treatment,the number of RGCs was lower than that in RIRI group(p<0.05).Expression of Cytochrome C: Western blot showed that the level of Cytochrome C expression was low in Sham group.Rats in RIRI group showed higher level of Cytochrome C expression.After Idebenone treatment,the level of Cytochrome expression was lower than that in RIRI group.The number of THY1-1 positve RGCs: After RIRI operation,the number of RGCs was increased.After Idebenone treatment,the number of RGCs was lower than that in RIRI group(p<0.05).Conslusions1.RIRI can induce higher level of Cytochrome C and Caspase-3 expression,lower number of RGCs.2.Idebenone can inhibit the expression of Cytochrome C and Caspase 3 and promote the survival of RGCs.