灵长类动物自发性年龄相关眼病动物模型的探讨

Experimental primate animal models for age related spontaneous eye diseases

目的本研究筛查老年猴群中自然产生的白内障,年龄相关性黄斑变性,糖尿病视网膜病变等眼病,通过对比灵长类动物眼底疾病改变与人类眼底疾病改变,探讨在老年猴群中建立年龄相关性眼病实验动物模型的可行性。方法 39只食蟹猴,平均年龄(11.9±2.05)岁,最小9岁,最大17岁和13只猕猴,平均年龄(15.5±5.2)岁,最小7岁,最大24岁,进行空腹血糖和2 h糖耐量检测。应用裂隙灯、眼底相机、眼压计初步筛查眼病和眼压值,疑似病例应用频域光学相干断层扫描(spectral-domain optical coherence tomography,SD-OCT)对视网膜病变进行确诊。结果血糖筛查中发现4例食蟹猴,3例猕猴血糖升高,眼底未发现类似人类糖尿病视网膜病变的相关病理改变。13只食蟹猴和6只猕猴出现不同程度的晶状体混浊。食蟹猴眼压均值为右眼(15.98±3.315)mm Hg(1 mm Hg=0.133 k Pa),左眼(15.82±4.021)mm Hg;猕猴眼压右眼(14.9±3.867)mm Hg,左眼(14.7±3.329)mm Hg。1例食蟹猴出现高眼压,眼底有早期青光眼改变。眼底图像筛查中,发现2例食蟹猴眼底出现散在玻璃膜疣分布于视网膜周围部。1例食蟹猴单眼出现地图样脉络膜病变。结论在老年猴筛查中发现了自发形成的晶状体混浊、视网膜玻璃膜疣以及脉络膜萎缩等年龄相关性眼病,证实了灵长类动物与人类有着相似的病理生理改变。同时未见与人类相似的糖尿病视网膜病变眼底改变,可能由于灵长类动物因高血糖引起的微血管结构改变与人类不同,或糖尿病尚未产生视网膜病变,为年龄相关性眼病灵长类动物模型提供了依据。

Objective To screen the pathologic changes of retina of old monkeys to establish a spontaneous eye disease model for age related eye diseases. Methods Thirty-nine cynomolgus monkeys （age：11.9±2.05, min=9; max=17） and 13 macaques （age：15.5±5.2, min=7; max=24） were used to perform eye examination including fundus, and intraocular pressure（IOP）. Blood glucose was evaluated through glucose tolerance test （GTT）. Non-mydriatic fundus camera was used to examine the pathogenic changes of retinal, the suspicious cases were then imaged by spectral-domain optical coherence tomography （SD-OCT） to evaluate the retinal structure. Results Three macaques and four cynomolgus were hyperglycemic, no diabetic retinopathy symptoms were any of the found in three animal. Thirteen cynomolgus and 6 macaques showed lens opacity in both eyes. The average IOP of cynomolgus was oculus dexter （OD）：（15.98±3.315）mmHg （1 mmHg=0.133 kPa）,oculus sinister （OS）：（15.82±4.021）mmHg. The average IOP of macaque was OD：（14.9±3.867）mmHg, OS：（14.7±3.329）mmHg.One cynomolgus has high IOP in both eyes; fundus photo displayed an early change of glaucoma symptom. Fundus photography from 2 monkeys both eyes showed numerous drusen distributing throughout the whole retina. One retina displayed geographic serpiginous choroiditis in right eye.Conclusion In old monkeys eyes, macular degeneration, cataract, and glaucoma were observed with the symptom similar to those of human being. But no diabetic retinopathy （DR） symptoms was found in hyperglycemic cases, which may because the different pathologic change in primate animal or the pathologic change haven＇t occurred. Our study provided a primate animal source with spontaneous age related eye disease for studying the novel therapeutic agents or cell therapy for clinical trial.