Characterization of a monkey model with experimental retinal damage induced by N-methyl-D-aspartate.

IF 4 3区 医学 Q2 CELL BIOLOGY Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-07-26 DOI:10.1242/dmm.050033
Guo Liu, Longxiang Huang, Junkai Tan, Yun Wang, Chunlin Lan, Yaxi Chen, Yukai Mao, Xizhen Wang, Ning Fan, Yihua Zhu, Xianjun Zhu, Xuyang Liu
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Abstract

N-methyl-D-aspartate (NMDA)-induced retinal damage has been well studied in rodents, but the detailed mechanisms have not yet been characterized in nonhuman primates. Here, we characterized the retinal degenerative effects of NMDA on rhesus monkeys in vivo. NMDA saline or saline-only control was injected intravitreally to the randomly assigned eyes and contralateral eyes of four rhesus monkeys, respectively. The structural and functional changes of retina were characterized by optical coherence tomography and electroretinography on days 0, 4, 30 and 60 post injection. Both optic discs and macular areas of the NMDA-injected eyes initially presented with a transient retinal thickening, followed by continued retinal thinning. The initial, transient retinal thickening has also been observed in glaucoma patients, but this has not been reported in rodent NMDA models. This initial response was followed by loss of retina ganglion cells (RGCs), which is similar to glaucomatous optic neuropathy and other RGC-related retinal degenerations. The amplitudes of both the photopic negative response and pattern electroretinogram decreased significantly and remained low until the end of the study. Thus, the NMDA monkey model may serve as a more clinically relevant animal model of retinal damage.

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N-甲基-D-天冬氨酸诱导的实验性视网膜损伤猴子模型的特征。
N-甲基-D-天冬氨酸(NMDA)诱导的视网膜损伤已在啮齿类动物中进行了深入研究,但其在非人灵长类动物中的详细机制尚未确定。在这里,我们描述了 NMDA 对恒河猴视网膜退化效应的活体特征。我们分别向四只恒河猴随机分配的眼睛和对侧眼玻璃体内注射了 NMDA 生理盐水或仅含生理盐水的对照组。注射后第 0、4、30 和 60 天,通过光学相干断层扫描和视网膜电图观察视网膜的结构和功能变化。NMDA注射眼的视盘和黄斑区最初都出现了短暂的视网膜增厚,随后视网膜持续变薄。在青光眼患者中也观察到了最初的一过性视网膜增厚,但在啮齿类 NMDA 模型中尚未见报道。最初的反应之后是视网膜神经节细胞(RGC)的丧失,这与青光眼性视神经病变和其他与 RGC 相关的视网膜变性相似。光视负反应和模式视网膜电图的振幅都显著下降,并且直到研究结束都保持在较低水平。因此,NMDA猴模型可能是一种更贴近临床的视网膜损伤动物模型。
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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