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Guoge Han, Pinghui Wei, Meiqin He, Yanhua Chu; Targeting Warburg effect: Metabolic characterization of human aqueous humor in relation to age related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1698.
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© ARVO (1962-2015); The Authors (2016-present)
The retina has high energy demand and a propensity of “aerobic glycolysis” known as the Warburg effect. Energy compromise is part of the pathogenesis in wet age related macular degeneration (wAMD). However, whether the Warburg effect is correlated to this disease remains unclear. Metabolomics was employed in characterization of aqueous humor (AH) and firstly in revealing the Warburg effect metabolic signatures in wAMD patients. We hypothesize that retina is able to upregulate glycolytic lactate and to decrease oxidative pathway as an adaptive response in the presence of ischemic retinal injury.
The AH samples were collected from 40 patients. Participants who were diagnosed with wAMD (n=20) served as the patients group and those with cataract surgery served as a control group (n=20). Patients who have had diabetes mellitus, hypertension or received intravitreal injection at the time of enrollment, were excluded. Gas chromatographies, coupled with time-of-flight mass spectrometers (GC/TOF MS), were performed in identifying AH in the purpose of nontargeted and quantification metabolomic analysis in this study. PLS-DA, SIMCA-P and SPSS21.0 were employed to determine the significant change of metabolites.
35 metabolites in relation to Warburg effect were identified in AH from a set of 40 patients. Further statistical analysis showed that 4 metabolites were significantly changed (Variable important for the projection, VIP≥1 and p≤0.05). Lactate was significantly increased in wAMD groups compared to control (p=0.04), showing upregulation of glycolysis pathway. A significantly decrease of succinic acid was observed corresponding to a 25.45% decrease in wAMD compared to controls (p=0.02), indicating the presence of retinal mitochondrial impairment. No significant difference was found in other Krebs cycle metabolites (Pyruvic acid, Malate) as well as glucose between the control and wAMD patients (p≥0.05).
Our results are consistent with the hypothesis that the Warburg effect is involved in metabolic characterization in relation to wAMD. Further research will be needed to investigate either succinic acid formation or transformation enzymes changes are accountable for decreased succinic aicd in wAMD patients. These findings would offer novel treatments for fighting AMD from neuroprotection perspective.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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