Fig. 1. NRTIs block Alu-induced RPE degeneration and Caspase-1 activation.
(A, B) Fundus photographs (top row) and flat mounts stained for zonula occludens-1 (ZO-1; red) (bottom row) of mice injected sub-retinally with control (pNull) or Alu RNA-expressing (pAlu) plasmids and (A) once daily oral administration of d4T (150 mg/kg/day) or (B) twice daily intraperitoneal administration of AZT (100 mg/kg/day). In fundus photographs degeneration outlined by blue arrowheads. RPE degeneration prevented in (A) 5/6 (d4T) vs. 0/6 (vehicle) eyes; P = 0.015 and (B) 8/9 (AZT) vs. 0/8 (vehicle) eyes; P = 0.0004 by Fisher’s exact test (pAlu vs. pAlu + d4T or AZT). Scale bars, 50 μm. See also fig. S1. (C) Western blot of Caspase-1 activation (p20 subunit) or p45 pro-form and IRAK4 phosphorylation in primary human RPE cells transfected with Alu RNA ± d4T (100 μM). Fold change in densitometry compared to mock. (D) Western blot of Caspase-1 pro (p45) and active (p20) forms in human RPE cells transfected with Alu RNA ± NRTIs (3TC, AZT, ABC) (100 μM). Fold change in densitometry compared to mock. Images representative of n = 3–4 (A, B), n = 6–9 (C, D).