PDF(Pubmed)
Abstract：
Mutations in the photoreceptor-specific C2orf71 gene (also known as photoreceptor cilium actin regulator protein PCARE) cause autosomal recessive retinitis pigmentosa type 54 and cone-rod dystrophy. No treatments are available for patients with C2orf71 retinal ciliopathies exhibiting a severe clinical phenotype. Our understanding of the disease process and the role of PCARE in the healthy retina significantly limits our capacity to transfer recent technical developments into viable therapy choices. This study summarizes the current understanding of C2orf71-related retinal diseases, including their clinical manifestations and an unclear genotype-phenotype correlation. It discusses molecular and functional studies on the photoreceptor-specific ciliary PCARE, focusing on the photoreceptor cell and its ciliary axoneme. It is proposed that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane during the development of a new outer segment disk in photoreceptor cells. This review also introduces various cellular and animal models used to model these diseases and provides an overview of potential treatments.
摘要：
光感受器特异性C2orf71基因（也称为光感受器纤毛肌动蛋白调节蛋白PCARE）的突变导致常染色体隐性遗传性视网膜色素变性54型和视锥细胞营养不良。对于具有表现出严重临床表型的C2orf71视网膜纤毛病变的患者没有可用的治疗方法。我们对疾病过程和PCARE在健康视网膜中的作用的理解极大地限制了我们将最新技术发展转化为可行的治疗选择的能力。这项研究总结了目前对C2orf71相关视网膜疾病的认识，包括其临床表现和不清楚的基因型-表型相关性。它讨论了光感受器特异性纤毛PCARE的分子和功能研究，专注于感光细胞及其睫状轴突。有人提出PCARE是一种肌动蛋白相关蛋白，与WASF3相互作用，以调节感光细胞中新的外节盘发育过程中纤毛膜的肌动蛋白驱动的扩张。这篇综述还介绍了用于模拟这些疾病的各种细胞和动物模型，并概述了潜在的治疗方法。
