Pharmaceutical Induction of PGC-1α Promotes Retinal Pigment Epithelial Cell Metabolism and Protects against Oxidative Damage

Figure 2

ZLN005 enhances mitochondrial respiration and upregulates OXPHOS targets. (a) Oxygen consumption rate (OCR) of ARPE-19 treated with 10 μM ZLN005 measured by the Seahorse Bioanalyzer. Oligomycin (Oligo, 1 mM), FCCP (500 nM), and rotenone and antimycin A (RA, 2 mM) were injected at the marked intervals. (b) Bioenergetics profiling confirmed that 5–20 μM ZLN005 efficiently increases basal and maximal RPE respiration. RPE spare capacity was significantly increased with 5 and 10 μM ZLN005 (veh, ; 5 μM, , 10 μM, , 20 μM, , ANOVA). (c) OXPHOS genes, ATP50, COX4, COX5b, and NDUFB5, are significantly upregulated (veh, for all genes; ZLN, for all genes). (d) Relative expression of PGC-1β, FOXO1, and PPARα increase (veh, for all genes; ZLN, for all genes). All gene expression data was analyzed using Student’s t-test. Statistical significance is represented as follows: , , , and .

(a)

(b)

(c)

(d)