先天性遗传性角膜内皮营养不良的病因及治疗进展

Advances in etiologies and management of congenital hereditary endothelial dystrophy

先天性遗传性角膜内皮营养不良(congenital hereditary endothelial dystrophy,CHED)是一种罕见的原发于角膜内皮的常染色体隐性遗传病,临床特征为出生时或生命早期出现双侧弥漫性角膜水肿和混浊。SLC4A11突变在CHED的发病机制中的作用是近年来的研究热点和难点。除SLC4A11外,其他潜在的CHED的致病基因如MPDZ也需被考虑。了解SLC4A11及其他可能致病基因在CHED中的作用及相关机制是未来重要的研究方向。目前除角膜移植术外,无其他有效的治疗方法。组织工程角膜内皮细胞移植和ROCK抑制剂的使用成为扩大供体组织来源的一种积极方式,在CHED治疗上具有一定的应用前景。随着有关CHED的分子遗传学和病理生理学的进展,更加低创、低成本的非手术的个性化治疗将有可能实现对CHED的早期干预,并在未来成为CHED的主要治疗方向。其中,非甾体抗炎药、SLC4A11-EL3工程蛋白、促进线粒体ROS清除的药物可能对相应患者人群的治疗有效,但需进一步验证。筛选符合不同治疗方法条件的合适患者人群同样十分重要。

Congenital hereditary endothelial dystrophy(CHED)is a rare autosomal recessive disorder of the corneal endothelium characterized by nonprogressive bilateral corneal edema and opacification present at birth or shortly thereafter.The role of SLC4A11 in the pathogenesis of CHED has been one of highlights and difficulties in recent years.In addition to SLC4A11,other potential pathogenic genes for CHED,such as MPDZ,should also be considered.Understanding the role of SLC4A11 and other potential pathogenic genes in the pathogenesis of CHED is an important research direction in the future.At present,the only definitive treatment for corneal endothelial dysfunction is corneal transplantation.Transplantation of tissue-engineered corneal endothelial cells and the use of Rho-associated kinase inhibition has become a positive way to expand the source of donor tissue,which has a certain application prospect in the treatment of CHED.With the development of molecular genetics and pathophysiology of CHED,it is possible that individualized non-surgical treatment with lower trauma and lower cost will realize early intervention of CHED and become the main treatment direction of CHED in the future.Non-steroidal anti-inflammatory drug,engineered SLC4A11-EL3-containing protein and drugs promoting mitochondrial ROS clearance may be effective for different patients,but further verification is needed.It is also very important to screen suitable patients for different treatment methods.