Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB, Canada.
Rev Physiol Biochem Pharmacol. 2020;178:41-81. doi: 10.1007/112_2020_39.
The cornea, the eye's outermost layer, protects the eye from the environment. The cornea's innermost layer is an endothelium separating the stromal layer from the aqueous humor. A central role of the endothelium is to maintain stromal hydration state. Defects in maintaining this hydration can impair corneal clarity and thus visual acuity. Two endothelial corneal dystrophies, Fuchs Endothelial Corneal Dystrophy (FECD) and Congenital Hereditary Endothelial Dystrophy (CHED), are blinding corneal diseases with varied clinical presentation in patients across different age demographics. Recessive CHED with an early onset (typically age: 0-3 years) and dominantly inherited FECD with a late onset (age: 40-50 years) have similar phenotypes, although caused by defects in several different genes. A range of molecular mechanisms have been proposed to explain FECD and CHED pathology given the involvement of multiple causative genes. This critical review provides insight into the proposed molecular mechanisms underlying FECD and CHED pathology along with common pathways that may explain the link between the defective gene products and provide a new perspective to view these genetic blinding diseases.
角膜是眼睛的最外层，可保护眼睛免受环境侵害。角膜的最内层是一层内皮细胞，将基质层与房水隔开。内皮细胞的一个主要作用是维持基质的水合状态。如果不能维持这种水合作用，就会损害角膜的透明度，从而影响视力。两种内皮性角膜营养不良，即 Fuchs 内皮性角膜营养不良（FECD）和先天性遗传性内皮性角膜营养不良（CHED），是致盲性角膜疾病，不同年龄的患者临床表现各不相同。隐性 CHED 起病早（通常在 0-3 岁），显性遗传 FECD 起病晚（40-50 岁），其表型相似，但病因是几个不同基因的缺陷。鉴于多个致病基因的参与，提出了一系列分子机制来解释 FECD 和 CHED 的发病机制。本综述深入探讨了 FECD 和 CHED 发病机制的潜在分子机制，以及可能解释缺陷基因产物之间联系的共同途径，为研究这些遗传性致盲疾病提供了新的视角。
