Matsuo Toshihiko, Sugimoto Kohei, Miyaji Mary, Hosoya Osamu, Ueda Masashi, Kobayashi Ryosuke, Horii Takuro, Hatada Izuho
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8558, Japan.
Department of Ophthalmology, Okayama University Hospital, Okayama 700-8558, Japan.
Biomedicines. 2024 Feb 5;12(2):370. doi: 10.3390/biomedicines12020370.
Strabismus, a neuro-ophthalmological condition characterized by misalignment of the eyes, is a common ophthalmic disorder affecting both children and adults. In our previous study, we identified the microsomal glutathione -transferase 2 () gene as one of the potential candidates for comitant strabismus susceptibility in a Japanese population. The gene belongs to the membrane-associated protein involved in the generation of pro-inflammatory mediators, and it is also found in the protection against oxidative stress by decreasing the reactivity of oxidized lipids. To look for the roles of the gene in the development, eye alignment, and overall morphology of the eye as the possible background of strabismus, gene knockout (KO) mice were generated by CRISPR/Cas9-mediated gene editing with guide RNAs targeting the exon 2. The ocular morphology of the KO mice was analyzed through high-resolution images obtained by a magnetic resonance imaging (MRI) machine for small animals. The morphometric analyses showed that the height, width, and volume of the eyeballs in KO homozygous mice were significantly greater than those of wild-type mice, indicating that the eyes of KO homozygous mice were significantly enlarged. There were no significant differences in the axis length and axis angle. These morphological changes may potentially contribute to the development of a subgroup of strabismus.
斜视是一种以眼睛不对视为特征的神经眼科疾病,是一种影响儿童和成人的常见眼科疾病。在我们之前的研究中,我们确定微粒体谷胱甘肽 -S-转移酶2(MGST2)基因是日本人群中共同性斜视易感性的潜在候选基因之一。MGST2基因属于参与促炎介质生成的膜相关蛋白,并且还通过降低氧化脂质的反应性在抗氧化应激中发挥作用。为了探究MGST2基因在眼睛发育、眼位对准以及作为斜视可能背景的眼睛整体形态中的作用,通过CRISPR/Cas9介导的基因编辑,使用靶向MGST2外显子2的引导RNA生成了MGST2基因敲除(KO)小鼠。通过小型动物磁共振成像(MRI)机器获得的高分辨率图像分析了KO小鼠的眼部形态。形态计量分析表明,MGST2 KO纯合小鼠眼球的高度、宽度和体积显著大于野生型小鼠,这表明MGST2 KO纯合小鼠的眼睛明显增大。眼轴长度和轴角没有显著差异。这些形态变化可能潜在地导致斜视亚组的发生。