Singh Grewal Simranjeet, Smith Joseph J, Carr Amanda-Jayne F
UCL Institute of Ophthalmology, University College London, London, UK.
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Ther Adv Ophthalmol. 2021 Feb 27;13:2515841421997191. doi: 10.1177/2515841421997191. eCollection 2021 Jan-Dec.
Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that typically affect the macular region, an area synonymous with central high acuity vision. This spectrum of disorders is caused by mutations in bestrophin1 (), a protein thought to act as a Ca-activated Cl channel in the retinal pigment epithelium (RPE) of the eye. Although bestrophinopathies are rare, over 250 individual pathological mutations have been identified in the gene, with many reported to have various clinical expressivity and incomplete penetrance. With no current clinical treatments available for patients with bestrophinopathies, understanding the role of in cells and the pathological pathways underlying disease has become a priority. Induced pluripotent stem cell (iPSC) technology is helping to uncover disease mechanisms and develop treatments for RPE diseases, like bestrophinopathies. Here, we provide a comprehensive review of the pathophysiology of bestrophinopathies and highlight how patient-derived iPSC-RPE are being used to test new genomic therapies in vitro.
贝斯特蛋白病是一组临床上有明显区别的遗传性视网膜营养不良症，通常会影响黄斑区，该区域是中央高敏锐度视觉的同义词。这种疾病谱是由贝斯特蛋白1（Bestrophin1）基因突变引起的，Bestrophin1是一种被认为在眼睛视网膜色素上皮（RPE）中作为钙激活氯通道发挥作用的蛋白质。尽管贝斯特蛋白病很罕见，但在该基因中已鉴定出超过250种个体病理突变，许多突变据报道具有各种临床表型和不完全外显率。由于目前尚无针对贝斯特蛋白病患者的临床治疗方法，了解Bestrophin1在细胞中的作用以及疾病背后的病理途径已成为当务之急。诱导多能干细胞（iPSC）技术有助于揭示疾病机制并开发针对RPE疾病（如贝斯特蛋白病）的治疗方法。在此，我们全面综述了贝斯特蛋白病的病理生理学，并强调了如何利用患者来源的iPSC-RPE在体外测试新的基因组疗法。
