Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide. Its main clinical signs are an accelerated decrease in the number of endothelial cells, thickening of Descemet’s membrane and formation of guttae in the extracellular matrix. The cornea’s ability to maintain stromal dehydration is impaired, causing painful epithelial bullae and loss of vision at the point when the amount of corneal endothelial cells cannot be compensated. At present, apart from corneal transplantation, there is no other effective treatment that prevents blindness. In this review, we first summarized the mutations of COL8A2, TCF4, TCF8, SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy. The molecular mechanisms associated with Fuchs endothelial corneal dystrophy, such as endoplasmic reticulum stress and unfolded protein response pathway, oxidative stress, mitochondrial dysregulation pathway, apoptosis pathway, mitophagy, epithelial-mesenchymal transition pathway, RNA toxicity and repeat-associated non-ATG translation, and other pathogenesis, were then explored. Finally, we discussed several potential treatments related to the pathogenesis of Fuchs endothelial corneal dystrophy, which may be the focus of future research. The pathogenesis of Fuchs endothelial corneal dystrophy is very complicated. Currently, corneal transplantation is an important method in the treatment of Fuchs endothelial corneal dystrophy. It is necessary to continuously explore the pathogenesis of Fuchs endothelial corneal dystrophy and establish the scientific foundations for the development of next-generation corneal therapeutics.

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Fuchs角膜内皮营养不良的基因突变及分子机制

Fuchs角膜内皮营养不良是一种遗传性疾病，是全世界角膜移植最常见的原因。其主要临床症状是内皮细胞数量加速减少、后弹力膜增厚和在细胞外基质中形成牙胶。角膜维持基质脱水的能力受损，导致疼痛的上皮大疱和角膜内皮细胞数量无法补偿时的视力丧失。目前，除角膜移植外，没有其他有效的预防失明的治疗方法。在这篇综述中，我们首先总结了Fuchs角膜内皮营养不良中COL8A2、TCF4、TCF8、SLC4A11和AGBL1基因的突变。与 Fuchs 角膜内皮营养不良相关的分子机制，然后探讨了内质网应激和未折叠蛋白反应通路、氧化应激、线粒体失调通路、细胞凋亡通路、线粒体自噬、上皮-间质转化通路、RNA毒性和重复相关的非ATG翻译等发病机制。最后，我们讨论了与 Fuchs 角膜内皮营养不良发病机制相关的几种潜在治疗方法，这可能是未来研究的重点。Fuchs角膜内皮营养不良的发病机制非常复杂。目前，角膜移植是治疗Fuchs角膜内皮营养不良的重要方法。有必要不断探索Fuchs角膜内皮营养不良的发病机制，为开发下一代角膜治疗药物奠定科学基础。