Fig. 5: The pyruvate dehydrogenase kinase isoform 4 (PDK4) inhibitor GM10395 suppresses proinflammatory cytokines and alleviates laser-induced choroidal neovascularization (CNV).

A Grading of CNV lesions was conducted in fluorescein angiography images from the vehicle, dichloroacetate (DCA; 250 mg/kg), and GM10395 (1 mg/kg)-treated CNV mice 7 days following CNV induction (n = 5 mice/group). ***P < 0.001 versus vehicle, Chi-square. B CNV lesion size was calculated using choroidal flat-mounts. (n = 34 lesions/group). Scale bar: 100 μm. Data are expressed as mean ± SEM. *P < 0.05 versus vehicle. One-way ANOVA with Tukey’s multiple comparisons test. C Protein was isolated from retinal pigment epithelium (RPE)/choroid of the vehicle and GM10395 (1 mg/kg)-treated CNV mice 1 day after CNV induction. Lysates were subjected to immunoblotting for phosphorylated pyruvate dehydrogenase E1-alpha subunit (p-PDHE1α). The lanes were run on the same gel but were noncontiguous. Data are expressed as mean ± SEM. *P < 0.05 versus vehicle (n = 3/group). Two-tailed unpaired t-test. D mRNA levels of the proinflammatory cytokines interleukin-1 beta (Il1b), interleukin-6 (Il6), and monocyte chemoattractant protein-1 (Mcp1) were measured in the RPE/choroid of control mice, and vehicle- and GM10395 (1 mg/kg)-treated CNV mice 3 days after CNV induction. (n = 3/group). Data are expressed as mean ± SEM. ^###P < 0.001 versus control; *P < 0.05; **P < 0.01; ***P < 0.001 versus vehicle. One-way ANOVA with Tukey’s multiple comparisons test. HSP90, heat shock protein 90; NV, neovascularization; PDHE1α, pyruvate dehydrogenase E1-alpha subunit.