Ophthalmology Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, 08035 Barcelona, Spain.
Int J Mol Sci. 2023 Jun 26;24(13):10670. doi: 10.3390/ijms241310670.
Mutations in the photoreceptor-specific 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 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 -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.
突变在光感受器特异性基因（也称为光感受器纤毛肌动蛋白调节蛋白 PCARE）导致常染色体隐性遗传视网膜色素变性 54 型和 Cone-Rod 营养不良。对于表现出严重临床表型的视网膜纤毛病患者，尚无治疗方法。我们对疾病过程的理解以及 PCARE 在健康视网膜中的作用极大地限制了我们将最近的技术发展转化为可行的治疗选择的能力。本研究总结了与相关的视网膜疾病的当前认识，包括其临床表现和不明确的基因型-表型相关性。它讨论了针对光感受器特异性纤毛 PCARE 的分子和功能研究，重点是光感受器细胞及其纤毛轴丝。提出 PCARE 是一种与肌动蛋白相关的蛋白，它与 WASF3 相互作用，以调节在光感受器细胞中新的外节盘发育过程中纤毛膜的肌动蛋白驱动扩展。本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。
