September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Fumaric acid ester monomethyl fumarate suppresses inflammatory gene expression and Müller cell gliosis in retinal ischemia-reperfusion
Author Affiliations & Notes
  • Hongkwan Cho
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Zhenhua Xu
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Matthew J. Hartsock
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Elia J Duh
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Hongkwan Cho, None; Zhenhua Xu, None; Matthew Hartsock, None; Elia Duh, None
  • Footnotes
    Support  NIH Grant EY022383 (EJD) and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 105. doi:
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      Hongkwan Cho, Zhenhua Xu, Matthew J. Hartsock, Elia J Duh; Fumaric acid ester monomethyl fumarate suppresses inflammatory gene expression and Müller cell gliosis in retinal ischemia-reperfusion. Invest. Ophthalmol. Vis. Sci. 2016;57(12):105.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Dimethyl fumarate (DMF), a fumaric acid ester (FAE) compound that activates Nrf2, has recently been approved for the treatment of multiple sclerosis, based on its neuroprotective and anti-inflammatory effects. Our lab has shown a neuroprotective role for MMF, the primary metabolite of DMF, by demonstrating ERG b-wave recovery in retina in the mouse model of ischemia-reperfusion (I/R). The objective of this study was to determine if MMF exerts anti-inflammatory effects and reduces Müller cell gliosis in the mouse I/R model and the role of Nrf2 in mediating MMF action.

Methods : Retinal I/R was performed by elevating intraocular pressure to 90mmHg for 90 min. Wild-type and Nrf2 knockout mice were compared to assess the impact of Nrf2 loss of function. Mice were pre-treated with intraperitoneal injections of MMF or vehicle at 2 days, 1 day and 0 day before I/R. After I/R, mice were treated daily with MMF or vehicle until sacrificed at designated time points. Inflammatory gene expression was determined at 48 hrs after I/R. At 7 days, GFAP immunofluorescence was used to determine Müller cell gliosis.

Results : Forty-eight hours after I/R injury, MMF treatment significantly suppressed the expression of a battery of inflammatory genes in wild-type mice. Seven days after I/R, a significant increase in Müller cell gliosis was observed in the vehicle-treated group. This I/R-induced increase was significantly suppressed by MMF treatment. Importantly, MMF treatment did not show these effects in Nrf2 knockout mice, suggesting that these MMF effects were Nrf2-specific.

Conclusions : The results from this study indicate that MMF exerts an anti-inflammatory effect and reduces Müller cell gliosis in the retinal ischemia-reperfusion model in an Nrf2-dependent manner. Given that many major retinal diseases are associated with reactive Müller cell gliosis, these treatment effects of MMF could have broad implications for the treatment of multiple retinal pathologies

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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