Disease Mechanisms in Best Disease

 描述（由申请人提供）：贝斯特病或卵黄状黄斑营养不良是一种以进行性和不可逆的中心视力丧失为特征的人类黄斑变性疾病。这种疾病是由BEST 1基因中的一系列不同（主要是错义）突变引起的。目前没有治疗或治愈这种情况。在这个多中心，多PI的建议，我们将评估最好的疾病的病理生理学使用RPE细胞来源于诱导多能干细胞（iPSC）从已知BEST 1突变的患者。初步数据显示，这些细胞至少概括了患有Best疾病的人RPE细胞的一些表型。我们提出了多学科实验，这将导致更好地了解这种致盲性疾病，包括：确定Best疾病患者源性RPE细胞氯离子电导和细胞电生理学的病理学;确定不同突变之间的病理关系，以及Best疾病的显性和隐性形式之间的病理关系;并评估基因治疗/基因组编辑作为Best疾病的潜在治疗方法。这些重要的研究将为这种疾病的新疗法铺平道路。

 DESCRIPTION (provided by applicant): Best disease, or vitelliform macular dystrophy, is a human macular degenerative disorder characterized by progressive and irreversible central vision loss. The disease is caused by a host of different (largely missense) mutations in the gene BEST1. Currently there is no treatment or cure for this condition. In this multicenter, multi-PI proposal, we will evaluate the pathophysiology of Best disease using RPE cells derived from induced pluripotent stem cells (iPSCs) from patients with known BEST1 mutations. Preliminary data show that these cells recapitulate at least some the phenotypes of human RPE cells with Best disease. We propose multidisciplinary experiments that will lead to a better understanding of this blinding disease, and that include: determining the pathology of Best disease patient-derived RPE cell chloride conductance and cellular electrophysiology; determining the pathological relationship between different mutations, and between dominant and recessive forms of Best disease; and evaluating gene therapy/genome editing as a potential treatment for Best disease. These important studies will pave the way for new treatments for this disorder.