Fig. 6.

Model for AMD related changes in RPE. AMD is associated with mitochondrial dysfunction and a bioenergetic crisis, documented by decreased OxPhos and glycolysis. Mitochondrial dysfunction leads to increased ROS production. PGC1a and redox sensitive transcription factors (TF) respond to environmental changes caused by mitochondrial dysfunction. In combination with mitochondrial retrograde signaling, these pathways alter gene expression and protein content of the cell. The epigenetic landscape, denoted by CpG methylation (Me) adds another layer of complexity to gene expression, and is altered due to an oxidative challenge. These changes lead to an increased resistance to oxidative stress and an altered bioenergetics profile.