Age-related macular degeneration (AMD), a leading cause of blindness in the developed world, is characterized by the degeneration of retinal pigment epithelial (RPE) cells. In Cell, Ambati and colleagues identify a key role for activation of the NLRP3 inflammasome in the RPE cell death seen in AMD. They find that Alu RNA, an abundant noncoding retrotransposon-derived RNA species, triggers RPE cell death but is not recognized by any conventional sensors of nucleic acid, such as the various TLRs, RIG-I or Mda5. Furthermore, loss of the RNase Dicer1 results in the accumulation of Alu RNA in RPE cells and RPE cell death. This death seems to be unrelated to pyroptosis but requires NLRP3, caspase-1 and interleukin 18 (IL-18), and, notably, RPE cells from patients with AMD have higher expression of these inflammasome components. Dicer1 therefore seems to have a role independent of microRNA processing by preventing the accumulation of NLRP3 inflammasome–stimulatory Alu RNA.

Cell (11 May 2012) doi:10.1016/j.cell.2012.03.036