July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Monomethyl fumarate protects the retina in a mouse model of light-induced retinal degeneration
Author Affiliations & Notes
  • Dan Jiang
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Renee C. Ryals
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Samuel J. Huang
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
    Physiology and Pharmacology, OHSU, Portland, Oregon, United States
  • Kyle K. Weller
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Hope E. Titus
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Bryan M. Robb
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Firas W. Saad
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Ribal A. Salam
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Paul Yang
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Mark E Pennesi
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2486. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Dan Jiang, Renee C. Ryals, Samuel J. Huang, Kyle K. Weller, Hope E. Titus, Bryan M. Robb, Firas W. Saad, Ribal A. Salam, Paul Yang, Mark E Pennesi; Monomethyl fumarate protects the retina in a mouse model of light-induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2486.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Monomethy fumarate (MMF) is the biologically active metabolite of dimethyl fumarate (DMF), which has been FDA-approved for treating multiple sclerosis. MMF targets a profile of molecules implicated in geographic atrophy (GA) and inherited retinal degenerations. We studied the ability of MMF to elicit retinal neuroprotection using a mouse model of light-induced retinal degeneration (LIRD).

Methods : LIRD was induced by exposing albino BALB/c mice (8-10 weeks old male) to bright light (10,000 lux) for 1 hour. Before light exposure, MMF at doses ranging from 50 mg/kg to 100 mg/kg, or the same volume of 1xPBS as the vehicle, were injected intraperitoneally into BALB/c mice (n>9 in each group). Seven days after light exposure and injection, spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) were used to evaluate the retina structure and function. Real-time quantitative PCR was used to assess gene expression level changes in the neural retinas (n=6 per group) at 24 hours post-light exposure. One-way ANOVA (with Tukey’s multiple comparison tests) was used for statistical analysis among different groups.

Results : MMF significantly protected mouse retina from LIRD, both structurally and functionally. MMF-mediated retinal protection was dose-dependent, starting from a single dose of 50 mg/kg to ranging up to 100 mg/kg, which provided full protection without side effects. At 24 hours post-light exposure, the expression of the Hcar2 receptor, macrophages/microglia markers (Cd14, Cxcl11, Mrc1, Ccl22), proinflammatory genes (Nlrp3, Casp1, Il-1β, Tnf-α), and an anti-oxidative gene (Hmox1) were upregulated. Treatment with 100 mg/kg of MMF significantly attenuated or reversed the gene changes caused by LIRD.

Conclusions : This study provided evidence that MMF can completely protect the retina from LIRD in BALB/c mice. MMF-mediated neuroprotection involved modulation of genes associated with macrophage/microglia activation, oxidative stress, and inflammation. The neuroprotective effects suggested MMF as a potential candidate for the treatment of GA or inherited retinal degenerations.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×