Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, USA.
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
Methods Mol Biol. 2022;2549:219-231. doi: 10.1007/7651_2021_384.
Leber's Hereditary Optic Neuropathy is the most prevalent mitochondrial neurological disease caused by mutations in mitochondrial DNA encoded respiratory complex I subunits. Although the genetic origin for Leber's hereditary optic neuropathy was identified about 30 years ago, the underlying pathogenesis is still unclear primarily due to the lack of a relevant system or cell model. Current models are limited to lymphoblasts, fibroblasts, or cybrid cell lines. As the disease phenotype is limited to retinal ganglion cells, induced pluripotent stem cells will serve as an excellent model for studying this tissue-specific disease, elucidating its underlying molecular mechanisms, and identifying novel therapeutic targets. Here, we describe a detailed protocol for the generation of retinal ganglion cells, and also cardiomyocytes for proof of iPSC pluripotency.
Leber 遗传性视神经病变是最常见的线粒体神经系统疾病，由线粒体 DNA 编码的呼吸复合物 I 亚单位突变引起。尽管 Leber 遗传性视神经病变的遗传起源大约在 30 年前就已经确定，但由于缺乏相关的系统或细胞模型，其潜在的发病机制仍不清楚。目前的模型仅限于淋巴母细胞、成纤维细胞或杂种细胞系。由于疾病表型仅限于视网膜神经节细胞，诱导多能干细胞将成为研究这种组织特异性疾病的理想模型，阐明其潜在的分子机制，并确定新的治疗靶点。在这里，我们描述了生成视网膜神经节细胞的详细方案，以及用于证明 iPSC 多能性的心肌细胞。
