脉络膜视网膜变性：分子机制与治疗方法。

Choroideremia: molecular mechanisms and therapies.

机构信息

Development, Ageing, and Disease, University College London (UCL) Institute of Ophthalmology, London, EC1V 9EL, UK; Ocular Genomics and Therapeutics Laboratory, The Francis Crick Institute, London, NW1 1AT, UK; Department of Genetics, Moorfields Eye Hospital National Health Service (NHS) Foundation Trust, London, EC1V 2PD, UK; Department of Ophthalmology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.

出版信息

Trends Mol Med. 2022 May;28(5):378-387. doi: 10.1016/j.molmed.2022.02.011. Epub 2022 Mar 24.

DOI:10.1016/j.molmed.2022.02.011

PMID:35341685

Abstract

Choroideremia (CHM) is a monogenic X-linked chorioretinal dystrophy affecting the photoreceptors, retinal pigment epithelium (RPE), and choroid; it is caused by mutations involving the CHM gene. CHM is characterized by night blindness in early childhood, progressing to peripheral visual field loss and eventually to complete blindness from middle age. CHM encodes the ubiquitously expressed Rab escort protein 1 (REP1), which is responsible for prenylation of Rab proteins and is essential for intracellular trafficking of vesicles. In this review we explore the role of REP1 in the retina and its newly discovered systemic manifestations, and discuss the therapeutic strategies for tackling this disease, including the outcomes from recent clinical trials.

摘要

脉络膜视网膜变性（CHM）是一种单基因 X 连锁的脉络膜视网膜营养不良，影响感光细胞、视网膜色素上皮（RPE）和脉络膜；它是由涉及 CHM 基因的突变引起的。CHM 的特征是儿童早期出现夜盲症，随后发展为周边视野丧失，最终从中年起完全失明。CHM 编码广泛表达的 Rab 衔接蛋白 1（REP1），该蛋白负责 Rab 蛋白的异戊二烯化，对于囊泡的细胞内运输至关重要。在这篇综述中，我们探讨了 REP1 在视网膜中的作用及其新发现的全身表现，并讨论了治疗这种疾病的策略，包括最近临床试验的结果。