In this context, the next steps for fully characterising the regulatory role of PERK downregulation in ARPE-19 and further in AMD RPE need to focus on examining the induction and downstream signalling pathways of the other two major components of UPR, the IRE1 and ATF6, that also regulate ER stress, apoptosis and autophagy following PERK knockdown8,10,40. This evidence concerns the gene ERN1 and age-related macular degeneration.