Chemical chaperone decreased CHOP expression and mitigated CSE-induced apoptosis. ARPE-19 cells were pretreated with TMAO for 6 h, followed by CSE (320 μg/ml) treatment for 6–24 h. A, representative Western blots of p-eIF2α and eIF2α (CSE- treated for 6 h), ATF4 and CHOP (CSE-treated for 12 h), and cleaved-caspase-3 (CSE-treated for 24 h). B, densitometry analysis of p-eIF2α (normalized with eIF2α), ATF4, CHOP, and cleaved-caspase-3 (normalized with β-actin). C, apoptosis of ARPE-19 cells was examined by TUNEL assay after CSE 320 μg/ml 24 h treatment with or without TMAO (200 mm, 6 h) pretreatment. Scale Bar: 50 μm. D, quantification of TUNEL-positive cells. All data were expressed as mean ± S.D., from three independent experiments. *, p < 0.05; **, p < 0.01 versus Ctrl; †, p < 0.05; ‡, p < 0.01 versus CSE.