多模影像对糖尿病小鼠眼底特征的实验研究

Experimental study of fundus features of diabetic mice with multimodal imaging

目的观察糖尿病小鼠视网膜影像改变特征,为糖尿病小鼠视网膜病理改变特征提供影像学依据。方法8周龄C57BL/6J小鼠连续5 d腹腔注射链脲佐菌素STZ(50 mg/kg),1周后测量小鼠空腹血糖浓度,模型复制成功的糖尿病小鼠(模型组)与正常小鼠(对照组)喂养5个月,5个月后对正常小鼠和糖尿病小鼠进行双眼光学相干断层扫描/光学相干断层扫描血管造影(OCT/OCTA)及眼底荧光血管造影(FFA)检测,采用图湃软件和Image J软件得出眼底视网膜厚度,血管密度、形态及管径大小,以及荧光素渗漏情况等数据,最后用GraphPad Prism进行统计学分析。结果对照组内层内环视网膜厚度大于模型组(P<0.05),对照组内层中、外环及外层内、中、外环厚度与模型组比较,差异均无统计学意义(P>0.05)。对照组表层及深层内、中、外环视网膜血管密度与模型组比较,差异均无统计学意义(P>0.05)。对照组一、二级血管管径值均窄于模型组、(P<0.05)。应用多模影像技术可以明确糖尿病视网膜病变(DR)的具体部位及捕捉DR的病变特征,包括微血管瘤、视网膜薄变、小血管迂曲扩张,以及迂曲扩张的小血管周围毛细血管网间隙增宽和囊样暗腔样改变。结论OCT/OCTA及FFA的多模影像相结合,可以活体监测DR小鼠视网膜早期损伤及毛细血管早期特征改变,对DR基础研究发挥一定作用。

Objective The characteristics of retinal imaging changes in aged diabetic mice were observed by OCT/OCTA as well as FFA assays,which provided an imaging basis for the characteristics of pathological changes in the retina of diabetic mice.Methods The experimental method was to routinely feed C57BL/6J diabetic mice at 8 weeks of age with 5 consecutive days of intraperitoneal injection of STZ for 5 days and C57BL/6J normal mice at 8 weeks of age with intraperitoneal injection of normal saline for 5 consecutive days.After 5 months,all mice were tested with OCT/OCTA and FFA in both eyes,and the data of fundus retinal thickness,blood vessel density,morphology and tube diameter,and fluorescein leakage were obtained by Tupai software and Image J software,and finally statistical analysis was performed with GraphPad Prism software.This experiment meets the ethical requirements of experimental animals of Nanjing University of Chinese Medicine,ethics number 2022DW-333-02.Results The thickness of the inner inner-ring retina in the normal group was greater than that in the diabetic group,and the difference was statistically significant(P<0.05),while the thickness of the inner middle and outer rings and the outer inner and middle outer rings in the normal group did not differ significantly from that in the diabetic group,and none of them were statistically significant(P>0.05).The superficial and deep inner,middle,and outer retinal vessel densities in the normal group were not statistically different from those in the diabetic group(P>0.05).The values of primary and secondary vessel diameters in the normal group were narrower than those in the diabetic group,and the differences were statistically significant(P<0.05).In addition,the application of multimodal imaging technology can clarify the specific location of diabetic retinopathy(DR)and capture the characteristics of DR,including microangiomas,retinal thinning,tortuous dilatation of small blood vessels,and widening of the capillary network gaps and cystic dark-cavity-like changes around tortuous dilatation of small blood vessels.Conclusion Combined multimodal imaging with OCT/OCTA and FFA allows in vivo monitoring of early retinal damage and early capillary characterization in DR mice,playing a role in basic DR research.