As downregulated EIF2AK3 was documented in the RPE of AMD patients16, the findings outlined in this study in the model ARPE-19 system could suggest that in vivo, RPE in AMD may lose the ability to initiate the apoptotic program in response to accumulated misfolded proteins in the ER, possibly as a protective measure to ensure cellular survival of the post-mitotic RPE. This evidence concerns the gene EIF2AK3 and age-related macular degeneration.