Unfolded Protein Response in Fuchs Endothelial Corneal Dystrophy: A Unifying Pathogenic Pathway?

TL;DR: Genetic variation in TCF4 contributes to the development of FCD and is associated with typical and advanced FCD.

TL;DR: The TGC trinucleotide repeat expansion in TCF4 is strongly associated with FECD, and a repeat length >50 is highly specific for the disease, which suggests that trin nucleotide expansion may play a pathogenic role in the majority of FECD cases and is a predictor of disease risk.

TL;DR: This review expands upon the recent findings from proteomic and genetic studies and builds upon recent advances in understanding the causes of this common corneal disorder.

TL;DR: A complex interplay of genetic, epigenetic, and exogenous factors in inciting oxidative stress, auto (mito)phagy, unfolded protein response, and mitochondrial dysfunction during CEC degeneration is discussed.

TL;DR: The cloning of perk is described, a gene encoding a type I transmembrane ER-resident protein that contains a protein-kinase domain most similar to that of the known eIF2α kinases, PKR and HRI that implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.

TL;DR: The role of the molecules that are activated during the UPR is examined in order to identify the molecular switch from the adaptive phase to apoptosis and how the activation of these molecules leads to the commitment of death and the mechanisms that are responsible for the final demise of the cell.

TL;DR: A model in which the activity of UPR signaling pathways reflects the biosynthetic activity of the ER is proposed, which shows that this information is integrated into control of cellular events, which were previously not considered to be under control of ER signaling pathways.

TL;DR: There is a causal link between the duration of UPR branch signaling and life or death cell fate after ER stress, and key findings from studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa.