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. 2014 Oct 27;111(45):16082–16087. doi: 10.1073/pnas.1403814111

Fig. 1.

Fig. 1.

Caspase-8 is up-regulated in the RPE of human eyes with geographic atrophy and mouse eyes with DICER1/Alu RNA dysmetabolism. (A) Caspase-8 (blue) abundance is increased in the RPE of human eyes with geographic atrophy compared with normal age-matched eyes. (B) Immunoblotting shows that Alu RNA activates Caspase-8 in cultured human RPE cells 24 h after treatment. Caspase-8 active p10 fragment is 3.04 ± 0.67 fold higher in abundance in Alu RNA-treated cells. Fold change in active Caspase-8 levels compared with Mock treatment, normalized to Vinculin, as determined by densitometry (mean ± SEM), are reported below their respective bands. (C) Caspase-8 activity assays of RPE/choroid lysates of AAV1-BEST1-Cre-treated Dicer1f/f mice and Alu RNA-treated wild type mice reveal that Caspase-8 is activated by Dicer1 knockdown or Alu RNA delivery (n = 6 independent experiments, *P = 0.0004 and **P < 0.0001 by two-tailed Student t test). Images are representative of at least three independent experiments (A).