Figure 1 of Nanda, Mol Vis 2019; 25:295-310.


Figure 1. Pathomechanisms in FECD. Alterations in DNA, such as mutations or polymorphic variations, cause several deregulatory events. Post-transcriptional byproducts of expanded repeats in the TCF4 and DMPK genes sequester splice-machinery proteins (MBNL-1) that elevate RNA toxicity and mis-spliced transcript levels. Channel and pump proteins, such as SLC4A11, MCTs, NA+/K+ ATPases, and aquaporins, are sub-optimally functional, or show reduced surface density, which affect the basic endothelial pump–barrier function. Increased endoplasmic reticulum (ER) stress elicits unfolded protein response and oxidative stress, which cause mitochondrial fragmentation and DNA lesions. Cells produce excessive and abnormal extracellular matrix materials that thicken Descemet’s membrane and form guttae. Progressive escalation of these processes causes apoptosis, and depletes most of the endothelial population.