Age-related visual impairments and retinal ganglion cells axonal degeneration in a mouse model harboring OPTN (E50K) mutation.
Age-related visual impairments and retinal ganglion cells axonal degeneration in a mouse model harboring OPTN (E50K) mutation.
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OPTN (E50K) 突变小鼠模型中与年龄相关的视力障碍和视网膜神经节细胞轴突变性
DOI：
10.1038/s41419-022-04836-3
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发表时间：
2022-04-18
影响因子：
9
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Hou M;Shao Z;Zhang S;Liu X;Fan P;Jiang M;Zhao Y;Xiao R;Yuan H
视网膜神经节细胞（Retinalganglioncells，RGC）轴突是视网膜与大脑之间视觉信息的信号载体。因此，它们在许多视神经退行性疾病如青光眼中起重要作用。在与青光眼相关的遗传风险中，已知视神经磷酸酶（OPTN）基因中的E50 K突变在没有眼内压（IOP）升高的情况下导致青光眼，而相关的病理机制和神经问题仍有待进一步研究。在本研究中，通过CRISPR/Cas9介导的基因组编辑建立OPTN（E50 K）突变小鼠模型，并鉴定了与衰老相关的RGCs丢失和视觉功能障碍。在16个月大的E50 K小鼠中，与相同年龄的野生型（WT）小鼠相比，轴突运输减少。电镜结果显示3月龄E50 K小鼠视网膜神经节细胞轴突线粒体形态异常，且随年龄增长而加重。提示视网膜神经节细胞轴突损伤可能是OPTN（E50 K）突变的年龄相关性结果，在青光眼发病中起一定作用。本研究结果对NTG的靶向预防和治疗具有潜在意义。
Retinal ganglion cells (RGCs) axons are the signal carriers of visual information between retina and brain. Therefore, they play one of the important roles affected in many optic neurodegenerative diseases like glaucoma. Among the genetic risks associated with glaucoma, the E50K mutation in the Optineurin (OPTN) gene are known to result in glaucoma in the absence of increased intraocular pressure (IOP), whereas the relevant pathological mechanism and neurological issues remain to be further investigated. In this study, the OPTN (E50K) mutant mouse model was established through CRISPR/Cas9-mediated genome editing, and aging-related RGCs loss and the visual dysfunction were identified. In E50K mice 16 months old, the axonal transport decreased comparing to wild-type (WT) mice at the same age. Furthermore, results of electron microscopy demonstrated significant morphological anomaly of mitochondria in RGCs axons of young E50K mice 3 months old, and these changes were aggravated with age. These indicated that the damaged mitochondria-associated dysfunction of RGCs axon should play an etiological role in glaucoma as an age-related outcome of OPTN (E50K) mutation. The findings of this study have potential implications for the targeted prevention and treatment of NTG.
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影响因子：
6.1
作者：
Brady ST;Morfini GA
通讯作者：
Morfini GA
影响因子：
5.3
作者：
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影响因子：
168.9
作者：
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通讯作者：
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作者：
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15.9
作者：
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通讯作者：
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