July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Evidence that the AMPK activator, Metformin, induced protection of the retina and RPE through metabolic reprogramming
Author Affiliations & Notes
  • Lei Xu
    Ophthalmology, Univ of Florida, Gainesville, Florida, United States
  • Jianhai Du
    West Virginia University, Morgantown, West Virginia, United States
  • John D Ash
    Ophthalmology, Univ of Florida, Gainesville, Florida, United States
  • Footnotes
    Commercial Relationships   Lei Xu, None; Jianhai Du, None; John Ash, None
  • Footnotes
    Support  Funding support to JDA includes NIH R01EY016459-12, Foundation Fighting Blindness, and an unrestricted departmental grant from Research to Prevent Blindness, Inc. Training support to CJK includes NIH T32EY007132.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1186. doi:
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      Lei Xu, Jianhai Du, John D Ash; Evidence that the AMPK activator, Metformin, induced protection of the retina and RPE through metabolic reprogramming. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1186.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Our data have shown that metformin protects photoreceptors from light damage, delays inherited retinal degeneration, and protects the retinal pigmented epithelium (RPE) from sodium iodate-induced injury. Metformin is a known modifier of cellular metabolism, and the purpose of this study was to determine whether metformin induced protection was mediated by metabolic reprogramming in the retina and RPE

Methods : 6-8 weeks old BALB/cJ mice were divided into five groups: untreated (Control), metformin injection for 1 day (MF1d), 7 days (MF7d), metformin injection for 7 days followed by light damage (MFLD) and light damage only (LD). Metformin was injected subcutaneously at 300 mg/Kg/ day. To induce LD, mice were exposed to 1200 lux white light for 4 hours from 6pm to 10pm. Retinas and posterior cups were collected at 2 hours after metformin injection or 6 hours after light damage. Metabolomic analysis were performed using Liquid and Gas chromatography mass spectrum (LC-MS/MS and GC-MS). The data was analysed using MetaboAnalyst 3.0.

Results : LC-MS/MS and GC-MS detected 180 metabolites in retina and 156 metabolites in RPE. Metabolic intermediates including NADP, FAD, lactate, and leucine were regulated by light damage. In the retina glycolytic metabolites including 2-phosphoglyceric acid, Glucose-6-P, Fructose 1,6-Biphosphate, and phosphoenolpyruvate carboxykinase were upregulated with metformin. In the RPE, metabolic intermediates including glycine, cysteine, cystine, NADP, and lactate levels were reduced.

Conclusions : Metabolomic profiling demonstrated metformin regulate amino acid biosynthesis, fatty acid metabolism and glycolysis, while it targets different metabolic pathways in retina versus RPE. These data suggest that metabolic reprogramming can be an effective mechanism to promote neuroprotection in the retina and RPE.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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