REV-ERBα agonist protects against chemical (NaIO3)-induced RPE damage. (A) Representative fundus images of vehicle and SR9009 (100 mg/kg body weight)-treated WT mice at 7 days post-NaIO3 injection (40 mg/kg body weight, a medium dose to evaluate drug protection against RPE damage), with quantification of lesion area per fundus image for each group. Sample size: NaIO3 injection, n = 5 mice/group; fundus quantification, n = 10 images (eyes)/group. (B) TUNEL staining (green) and quantification of TUNEL positive RPE cells (arrows) in the cross-sections (peripheral regions) of vehicle- and SR9009-treated retinas at 7 days post-NaIO3 injection. Blue: DAPI staining. Scale bar: 10 μm. n = 15 images/group. (C) WT primary RPE cells were first challenged by PQ (0.5 mM, 4 h), followed by vehicle or SR9009 (1 μm, 24 h) treatment. Oxygen consumption rate (OCR) was then analyzed using Seahorse XFe96 extracellular flux analyzer. SR9009-treated RPE cells showed significantly improved basal and maximal respiratory capacity under oxidative stress compared to vehicle-treated cells. *: P < 0.05, **: P < 0.01, ***: P < 0.001, ****: P < 0.0001. Error bars indicate SD. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)