Retinal dysfunction induced in a mouse model of unilateral common carotid artery occlusion.

Retinal dysfunction induced in a mouse model of unilateral common carotid artery occlusion.
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单侧颈总动脉闭塞小鼠模型视网膜功能障碍。

DOI:
10.7717/peerj.11665
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发表时间:
2021
期刊:
影响因子:
2.7
通讯作者:
Kurihara T
Kurihara T
中科院分区:
生物学3区
文献类型:
--
作者:
Lee D;Jeong H;Miwa Y;Shinojima A;Katada Y;Tsubota K;Kurihara T

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视网膜缺血应激与多种视网膜血管疾病的发病机制有关。为了研究视网膜缺血的病理机制,非常需要可重复的、稳健的和具有临床意义的实验啮齿动物模型。以前,我们建立了一个稳定的慢性低灌注视网膜损伤的小鼠模型,永久性单侧颈总动脉闭塞(UCCAO),并证明慢性病理过程中缺血性视网膜闭塞后,然而,视网膜功能障碍和其他急性视网膜缺血性损伤的UCCAO仍然不清楚。在这项研究中,我们试图检查视网膜功能的变化,以及急性视网膜缺血性改变,如视网膜变薄,胶质细胞增生和细胞死亡后UCCAO。使成年小鼠(雄性C57 BL/6,6-8周龄)在右侧经受UCCAO,并且在手术后14天使用视网膜电描记术主要测量视网膜功能。此外,视网膜变薄,胶质细胞增生和细胞死亡分别采用光学相干断层扫描,免疫组化和TUNEL法进行了研究。在单侧右侧视网膜的功能缺陷开始被视为7天后闭塞。具体而言,b波的振幅显著降低,而a波的振幅受到轻微影响。14 d后,右侧视网膜各波振幅和振荡电位振幅均明显降低。尽管在所有眼睛中没有观察到视网膜厚度的显著变化,但在UCCAO后基本上观察到单侧右侧视网膜中的视网膜胶质增生和细胞死亡。沿着该模型中先前的视网膜缺血结果,UCCAO可刺激视网膜缺血,导致视网膜的功能、形态和分子变化。该模型可用于研究人类缺血性视网膜病变的病理机制,并且还可用于测试用于各种缺血性眼部疾病的新药。
Retinal ischemic stresses are associated with the pathogenesis of various retinal vascular diseases. To investigate pathological mechanisms of retinal ischemia, reproducible, robust and clinically significant experimental rodent models are highly needed. Previously, we established a stable murine model of chronic hypoperfusion retinal injuries by permanent unilateral common carotid artery occlusion (UCCAO) and demonstrated chronic pathological processes in the ischemic retina after the occlusion; however, retinal functional deficits and other acute retinal ischemic injuries by UCCAO still remain obscure. In this study, we attempted to examine retinal functional changes as well as acute retinal ischemic alterations such as retinal thinning, gliosis and cell death after UCCAO. Adult mice (male C57BL/6, 6–8 weeks old) were subjected to UCCAO in the right side, and retinal function was primarily measured using electroretinography for 14 days after the surgery. Furthermore, retinal thinning, gliosis and cell death were investigated using optical coherence tomography, immunohistochemistry and TUNEL assay, respectively. Functional deficits in the unilateral right retina started to be seen 7 days after the occlusion. Specifically, the amplitude of b-wave dramatically decreased while that of a-wave was slightly affected. 14 days after the occlusion, the amplitudes of both waves and oscillatory potentials were significantly detected decreased in the unilateral right retina. Even though a change in retinal thickness was not dramatically observed among all the eyes, retinal gliosis and cell death in the unilateral right retina were substantially observed after UCCAO. Along with previous retinal ischemic results in this model, UCCAO can stimulate retinal ischemia leading to functional, morphological and molecular changes in the retina. This model can be useful for the investigation of pathological mechanisms for human ischemic retinopathies and furthermore can be utilized to test new drugs for various ischemic ocular diseases.
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