Fig. 4.
ERK1/2 inhibition rescues mouse RPE cell death induced by DICER1 knockdown. (A) The ERK1/2 inhibitor PD98059, but not p38 (SB202190) or JNK inhibitor (SP600125), protects the RPE of Dicer1f/f mice from Dicer1 knockdown-induced degeneration after AAV1-BEST1-Cre administration. PD98059, but not SB202190 (p38 MAPK inhibitor) or SP600125 (JNK inhibitor), rescues viability of mouse (B) and human RPE cells (C) after DICER1 depletion. PD98059 inhibits Dicer1 knockdown-induced ERK1/2 activation in mouse and human RPE cells (D–F). Subretinal transfection of plasmid coding for full-length MAPKKK (MEK1) induces RPE degeneration in wild-type mouse (G). Values are mean ± SEM, n = 3 independent experiments, *P < 0.05 by ANOVA and post hoc Newman–Keuls test (B and C). Images are representative of three to four independent experiments (A and D–G).