Abstract
Purpose :
To investigate the inhibitory effect of thiamine analogue on choroidal neovascularization (CNV) model, mediated by anti-inflammatory effect and mitochondrial respiration in human retinal pigment epithelium (RPE).
Methods :
In laser induced CNV model, the effects of fursultiamine were assessed by the vascular leakage and CNV size. The inflammatory signaling was evaluated by qPCR, Western blot, and ELISA in both tissues and cells, which was measured by lactate production and oxygen consumption rate in LPS (endotoxin) treated APRE-19.
Results :
Fursultiamine significantly reduced the vascular leakage and neovascular lesion size along with inflammatory cytokines including IL-1β, IL-6, IL-8, TNF-α, and MCP-1 in choroid and retina. These anti-inflammatory effects of fursultiamine were correlated with the reduced proinflammatory cytokines and phosphorylation of NF-κB in APRE-19. Interestingly, fursultiamine significantly enhanced the spare and maximal mitochondrial respiration correlated with the reduced lactate production compared to LPS only. Likewise, hypoxia induced lactate production and inhibitory phosphorylation of pyruvate dehydrogenase and mitochondrial fission which were attenuated by fursultiamine treatment.
Conclusions :
Fursultiamine might be the therapeutics for neovascular age-related macular degeneration, validated by both anti-inflammatory responses and reduced metabolic reprogramming based on enhanced the oxidative phosphorylation in the mitochondria.
This is a 2020 ARVO Annual Meeting abstract.