Meesmann角膜上皮营养不良发病机制及治疗的研究进展

Research Advances in Pathogenesis and Treatment of Meesmann Epithelial Corneal Dystrophy

Meesmann角膜上皮营养不良(MECD)是一种罕见的常染色体显性遗传性疾病,其特征性表现为角膜上皮存在大量的微囊。角蛋白(KRT)3基因和KRT12基因杂合错义突变是MECD的主要致病机制,可导致细胞骨架蛋白KRT3和KRT12结构改变,进而导致角膜上皮和前弹力层发生病理性改变。目前,手术治疗是反复发作或症状严重的MECD患者的主要治疗方式,但易复发。而针对小干扰RNA、规律间隔成簇短回文重复序列(CRISPR)/CRISPR相关蛋白9基因编辑技术等的基因治疗在疾病模型中可以有效减少相应KRT12蛋白的表达。因此,未来应进一步深入研究MECD的发病机制以及基因技术在MECD治疗中的应用。

Meesmann epithelial corneal dystrophy(MECD)is a rare autosomal dominant genetic disorder characterized by the presence of numerous microcapsules in the corneal epithelium.The heterozygous missense mutation of keratin(KRT)3 and KRT12 genes is the main pathogenic mechanism of MECD,which causes the structural changes of cytoskeletal KRT3 and KRT12 to trigger a series of pathogenic mechanisms and ultimately lead to pathological changes in corneal epithelium and Bowman′s layer.At present,surgical treatment is the main treatment for the MECD patients with recurrent or severe symptoms,but it′s prone to recurrence.And gene therapy targeting small interfering RNA,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9 gene editing technology can effectively reduce the expression of corresponding KRT12 in the disease model.Therefore,the pathogenesis of MECD and the application of gene technology in the treatment should be further studied in the future.