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Objective To compare the rates and pathological features of diabetic keratopathy in mice induced by single high dose or multiple low dose streptozotocin (STZ) injections.Methods Eighty male C57BL/6 mice (6-8 weeks old) were randomly divided into 4 groups with each group contain 20 mice:normal control group,multiple low dose 1 month group and multiple low dose 3 months group (injected with 60 mg/kg STZ for 5 consecutive times),single high dose 1 month group (injected with 150 mg/kg STZ).The survival rate,model success rate,body weight,glycosylated hemoglobin (HbA1c) content were compared among different modeling group.The percentages of residual epithelial defect area were examined by fluorescein sodium staining after removal of central corneal epithelium.The expression of p-Akt,Sirt1 and Ki67 were evaluated by immunofluorescent staining.The corneal sensitivity were compared among different groups before corneal epithelial curettage,3,7,10 and 14 days after corneal epithelial curettage.The corneal subbasal nerve density at 14 days after corneal epithelial curettage were compared among different groups.This study complied with the declaration of ARVO Results The success rate of diabetic modeling in multiple low dose 1 month group,multiple low dose 3 months group and single high dose 1 month group was 90％,80％ and 70％,respectively.The HbA1c levels in the diabetic modeling groups were significantly higher than that in the normal control group (all at P＜0.05).The percentage of residual epithelial defect area 24 and 48 hours after corneal epithelial curettage in the multiple low dose 3 months group and single high dosc 1 month group were significantly higher than those in the normal control group (all at P＜0.05).The fluorescence intensity of p-Akt,Sirt1 and Ki67 in the multiple low dose 3 months group and single high dose 1 month group were stronger than those in the normal control group.There were no significant differences on corneal sensitivity and corneal nerve density between normal control and multiple low dose 3 months group before and 14 days after the corneal epithelial removal (all at P＞0.05).However,the corneal sensitivity and corneal nerve density were dramatically decreased in the multiple low dose 3 months group and single high dose 1 month group before and 14 days after the corneal epithelial removal,and there were significant differences compared with normal control group (all at P＜0.05).Conclusions The injection of 60 mg/kg STZ can not induce the features of diabetic keratopathy in mice within 1 month.However,the mice of both 1 month after 150 mg/kg STZ injection and 3 months after 60 mg/kg STZ injection appear the typical epithelial and nerve features of diabetic keratopathy,therefore can be the ideal animal models for research.
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Objective To observe the effects of repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs on vitreous macular interface (VMI) in patients with exudative age-related macular degeneration (AMD).Methods Retrospective study.Thirty-four exudative AMD patients who treated with intravitreal anti-VEGF drugs were included in this study.There were 26 males and 8 females.The age ranged from 50 to 80 years,with the average of (62.8± 8.35) years.The eyes with at least 6 treatments during the 1-year follow-up were taken as the study eyes,and the eyes with no anti-VEGF drug treatment were the control eyes.Optical coherence tomography (OCT) examination was used to observe the VMI status of both eyes before treatment.Vitreous macular adhesion (VMA),macular epiretinal membrane (MEM),and complete vitreous detachment (C-PVD) were defined as abnormalities in VMI.The VMA was classified as focal (≤ 1500 μrn) and broad (＞ 1500 μtm) depending on the diameter of the vitreous and macular adhesions on the OCT images.Before treatment,there were 12 eyes with abnormal VMI in study eyes,including 8 eyes with broad VMA,3 eyes with focal VMA,and 1 eye with MEM;12 eyes with abnormal VMI in control eyes:broad VMA in 7 eyes,focal VMA in 2 eyes,C-PVD in 2 eyes,and MEM in 1 eye.The average follow-up time after treatment was 16.4 months.During the follow-up period,OCT was performed monthly in a follow-up mode.Comparing the changes on VMI between before and after treatment in both eyes of patients,respectively.The chi-square test was used to compare the difference on VMI.Because the number of samples was ＜40,Fisher's exact test was used for the analysis.Results At the final follow-up,12 eyes with abnormal VMI in the study eyes,including 5 eyes with broad VMA,2 eyes with focal VMA,3 eyes with C-PVD,and 2 eyes with MEM.There were 6 eyes altered comparing with baseline.In the control eyes,there were 13 eyes with abnormal VMI,including 5 eyes with broad VMA,7 eyes with C-PVD,and 1 eye with MEM.A total of 6 eyes changed on VMI comparing with baseline.At the final follow-up,there was no significant difference on VMI changes between the study eyes and its corresponding control eyes (P=0.053).In all eyes,a total of 4 eyes changed from focal VMA to C-PVD at the final follow-up,accounting for 80.0％ of the total focal VMA;3 eyes changed from broad VMA to C-PVD,accounting for 21.4％ of the total broad VMA.Conclusions Repeated anti-VEGF treatment has little effect on VMI.Regardless of anti-VEGF therapy,eyes with focal VMA appears to be more prone to C-PVD than the broad one.