Sally Temple, from the Neural Stem Cell Institute, has applied a robust hiPSC differentiation protocol to retinal pigment epithelium (RPE) to understand molecular mechanisms underlying age-related macular degeneration (AMD) (Stanzel et al., 2014), a highly prevalent neurodegenerative disease affecting one in five people older than age 75. A characteristic sign of the early, dry form of AMD is the appearance of large extracellular deposits termed drusen in the macula. Proteomic analysis has demonstrated that drusen share many molecular characteristics with senile plaques in AD. Observing significantly higher expression of AMD and drusen-associated transcripts, particularly Aβ42 and Aβ40, in AMD iPSC-RPE than in controls, the group took a candidate-based approach and identified several small molecules that reduce AMD-associated transcripts in iPSC-RPE, in some cases irrespective of original AMD disease status. These findings suggest that this in vitro model may be valuable to identify dry AMD therapeutics.
