Clinical And Experimental Efficacy Of Vincamine Treatment On Nonarteritic Anterior Ischemic Optic Neuropathy

Part One Efficacy of Vincamine treatment in a rat model of anterior ischemic optic neuropathy(rAION)Objective:To investigate the potential neuroprotective effects of Vincamine in the photodynamic induced rat anterior ischemic optic neuropathy model(rAION).Methods:Ninety Sprague-Dawley(SD)male rats were randomly divided into 6 groups:(a)blank control group(n=15),and five rAION groups,including(b)rAION simple model group(simple model group,n=15),(c)intragastrical carboxymethylcellulose sodium administration group(NaCMC group,n=15),(d)intragastrical Vincamine administration group(Vincamine group,n=15),(e)intravitreal injection of the PI3K inhibitor LY294002 with intragastrical Vincamine administration group(IVT LY+Vincamine group,n=15),and(f)intravitreal DMSO injection with intragastrical Vincamine administration group(IVT DMSO+Vincamine group,n=15).RAION models were established by photodynamic induction.Intragastrical Vincamine and NaCMC were administered beginning the first day after photodynamic induction,and continued twice a day for the next 28 days.Intravitreal injection of the PI3K inhibitor LY294002 and DMSO was performed separately after photodynamic induction.Vincamine was administered the day after intravitreal injection.On the first and 28th day after photodynamic induction,we examined fundus photography(FP)and fluorescein angiography(FA),and measured the concentration of NO in rats' blood serum using a nitric oxide detection kit.Flash visual-evoked potentials(FVEP)were measured on the 28th day.Rats were sacrificed on the first and 28th day after induction for HE staining and toluidine blue staining.Retinal flat-mount immunofluorescence,RT-PCR,and Western blot analysis was performed on the 28th day.Results:The first day after photodynamic induction,optic swelling could be seen in all right eyes.There is generalized dye leakage from the optic disc in FFA arteriovenous phase,suggesting photodynamic induction successfully modeled rAION.There was obvious optic nerve atrophy in rAION model eyes compared to the blank control group on the 28th day,however FP and FFA images showed no difference in the degree of atrophy in Vincamine group and NaCMC group.Retinal flat-mount immunofluorescence revealed that Vincamine treatment significantly rescued the number of retinal ganglion cells(RGCs/mm2,1356±208,p=0.002),compared to NaCMC treatment(829 ± 199)after four weeks of intragastrical administration.Blocking PI3K activity reduced this effect;the IVT LY+Vincamine group showed fewer RGCs/mm2(915 ±165,p=0.044,)compared to the IVT DMSO+Vincamine group(1236 ±220).Functional assessment with FVEP analysis demonstrated that the P1 amplitude was higher in the Vincamine group(13.20 ± 3.71?V)compared with the NaCMC group(8.18 ± 2.65,p=0.009).After four weeks,serum NO concentration was higher in the three Vincamine administration groups,but there were no significant differences between these groups.Western Blot analysis demonstrated that the simple model group showed both decreased p-Akt and eNOS,whereas Vincamine treatment increased p-Akt and eNOS,relative to both the simple model group and the NaCMC group.PCR analysis showed significant differences in relative mRNA levels of eNOS between the Vincamine group,NaCMC group,and IVT LY+Vincamine group.Conclusion:Vincamine prevented the degeneration of the retinal ganglion cells in the rAION model.The PI3K/Akt/eNOS pathway may play an important role in the neurodegenerative process.Part Two Therapeutic effect and safety analysis of vincamine SR in nonarteritic anterior ischmic optic neuropathyObjective:To observe the clinical efficacy and safety of vincamine SR on nonarteritic anterior ischmic optic neuropathy(NAIO~N.Methods:42 patients(42 eyes)who were diagnosed with monocular onset NAION in acute stage in our eye center from January to September 2015 were divided into two groups.Routine treatment such as steroid pulse therapy and neurotrophic treatment were given to all of patients.Vincamine SR,a kind of oral medicine was added to the treatment group with 3 0mg twice a day for 3 months.The best corrected visual acuity(BCVA),visual field,P-VEP and OCT were analyzed before and after the treatment.Results:42 patients of 42 eyes were enrolled in our study.27 patients were in the treatment group,aged from 33 to 79 years old,the average value was(55.55 ± 11.83)years old.The control group has 15 patients,aged from 40 to 70 years old,the average value was(55.71 ± 10.06)years old.There were no statistical differences between the two groups in the baseline.After 3 months of the therapy,the visual acuity of the treatment group(55.6%)was more effective than the control group(33.3%).After the treatment,the MD value of the two groups were lower compared with the baseline,the difference was statistically significant(t=2.342,2.269,P=0.027,0.041).The difference of P-VEP amplitude and potential of the two groups before and after the treatment were not statistically significant.The thickness of nerve fiber layer and the thickness of the ganglion cell complex were all lower than the baseline,and the difference was statistically significant(P=0.000).The two groups of treatment were effective,the treatment group was better than the control group.Adverse events related to the treatment of vincamine SR have not been found.Conclusion:Vincamine SR is helpftul in the treatment of nonarteritic anterior ischemic optic neuropathy.