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目的:评估一种新型纳米神经营养因子复合物(NP-CNTFs)在非人灵长类动物眼内应用的安全性。方法:利用纳米工艺制备包裹睫状神经营养因子(CNTF)的纳米粒。选取3只成年雄性食蟹猴，单眼玻璃体腔注射10 μl NP-CNTFs(1 μg/μl)作为NP-CNTFs组，对侧眼注射等体积磷酸盐缓冲液作为对照组。在注射前、注射后第3天和第7天，对食蟹猴行常规眼前节检查以评估结膜充血、前房闪辉及前房细胞等眼部症状并评分；采用彩色眼底照相观察眼底情况；采用频域光学相干断层扫描(SD-OCT)检测视网膜形态结构及厚度。结果:所制备NP-CNTFs粒径为(317±3)nm，多分散性指数为0.042±0.015，Zeta电位为(－38.9±0.7)mV，具备较好的稳定性、生物利用度和生物相容性。眼前节检查显示，NP-CNTFs组在注射后第3天表现出较对照组稍明显的结膜充血、前房闪辉和前房细胞，但在注射后第7天基本恢复正常。NP-CNTFs组与对照组注射后第3天眼前节症状评分分别为(2.67±0.88)和(1.00±0.58)分，注射后第7天分别为(0.67±0.33)和(0.33±0.33)分，组间比较差异均无统计学意义( t＝2.50、1.00，均 P>0.05)。彩色眼底照相结果显示，NP-CNTFs组和对照组在注射后第7天眼底均正常，未见玻璃体混浊、玻璃体出血、视网膜出血或视盘水肿等异常改变。SD-OCT结果显示，NP-CNTFs组和对照组在注射后第7天均未见明显视网膜组织学改变。NP-CNTFs组和对照组视网膜神经纤维层厚度分别为(107.67±0.88)和(111.00±3.22)μm，黄斑中央凹厚度分别为(255.67±2.03)和(254.67±3.84)μm，组间比较差异均无统计学意义( t＝1.43、0.50，均 P>0.05)。 结论:新型纳米药物NP-CTNFs在食蟹猴眼内应用的安全性较好。

Objective:To evaluate the safety of a novel nanoparticle neurotrophic factor complex for intraocular application in non-human primates.Methods:Nanoparticles incorporated with ciliary neurotrophic factor (NP-CNTFs) were produced utilizing nanotechnology.Three adult male cynomolgus macaques were included and intravitreally injected with 10 μl NP-CNTFs at a concentration of 1 μg/μl into one of the two eyes, and these three eyes were designated as the NP-CNTFs group.The contralateral eyes received the same volume of phosphate buffered saline and were designated as the control group.Before the injection and on days 3 and 7 after the injection, routine clinical examinations of the anterior segment were performed to evaluate the ocular clinical symptoms such as conjunctival congestion, anterior chamber flare and cells.The fundus condition was observed by fundus photography.The morphological structure and thickness of retinas were detected by spectral domain-optical coherence tomography (SD-OCT).The use and care of animals were in accordance with the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health and the standards of Association for Assessment and Accreditation of Laboratory Animal Care.The study protocol complied with the ethics of laboratory animal welfare and was approved by Hubei Topgene Biotechnology Co., Ltd.(No.IACUC-2019-012).Results:The NP-CNTFs prepared in this study had a particle size of (317±3)nm, a polydispersity index of 0.042±0.015, and a zeta potential of (-38.9±0.7)mV, and exhibited relatively good stability, bioavailability, and biocompatibility.Clinical examinations revealed that the clinical manifestations of conjunctival congestion, anterior chamber flare and cells were slightly more obvious in the NP-CNTFs group at 3 days after injection compared to the control group, but basically returned to normal at 7 days after injection.The scores of anterior-segment clinical symptoms of the NP-CNTFs and control group were (2.67±0.88) and (1.00±0.58) at 3 days after injection, and (0.67±0.33) and (0.33±0.33) at 7 days after injection, respectively, with no statistical differences between them ( t=2.50, 1.00; both at P>0.05).Fundus photography showed normal fundus in both groups at 7 days after injection with no abnormal changes including vitreous opacity, vitreous hemorrhage, retinal hemorrhage or papilloedema.SD-OCT showed no significant histological changes in the retinas at 7 days after injection in both groups.The retinal nerve fiber layer thickness of the NP-CNTFs and control group were (107.67±0.88) and (111.00±3.22)μm, respectively, and the macular foveal thickness of the two groups were (255.67±2.03) and (254.67±3.84)μm, respectively, with no statistical differences between them ( t=1.43, 0.50; both at P>0.05). Conclusions:The complex NP-CNTFs shows good safety for intraocular application in cynomolgus macaques.