June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Dimethyl Malonate disrupts the development of recurrent herpetic stromal keratitis, but not primary herpes simplex keratitis
Author Affiliations & Notes
  • Nicholas Koh Baugnon
    Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Xiao-Tang Yin
    Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Patrick Stuart
    Saint Louis University School of Medicine, Saint Louis, Missouri, United States
  • Footnotes
    Commercial Relationships   Nicholas Baugnon, None; Xiao-Tang Yin, None; Patrick Stuart, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 438. doi:
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      Nicholas Koh Baugnon, Xiao-Tang Yin, Patrick Stuart; Dimethyl Malonate disrupts the development of recurrent herpetic stromal keratitis, but not primary herpes simplex keratitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):438.

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

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Abstract

Purpose : Ocular infection by Herpes Simplex Virus (HSV) causes inflammatory damage to the cornea. In some cases, HSV infection can lead to the progressive disease Herpetic Stromal Keratitis (HSK) due to recurrent reactivation of latent virus and subsequent corneal damage. Recent studies suggest that metabolic reprogramming plays a key role in the inflammatory response. Naive lymphocytes transition from relying on oxidative phosphorylation during quiescence and activation to primarily depending on glycolysis to meet the metabolic demands of effector cells. We tested the hypothesis that disruption of oxidative phosphorylation by Dimethyl Malonate (DMM) would decrease the inflammatory response in HSK.

Methods :
We infected the scarified corneas of C57BL/6 male and female mice with the RE strain of HSV. Infection was confirmed by corneal swabs that demonstrated viral shedding. For reactivation disease, latent HSV was reactivated at 6 weeks post infection by controlled doses of UV-B light. DMM was diluted in phosphate buffered saline (PBS), then dissolved in ophthalmologic ointment. Mice were treated topically with this ointment from day 3 to day 14 post infection and post reactivation. Controls were treated with plain ophthalmologic ointment. HSK severity was evaluated by clinical scoring of corneal opacity (O), neovascularization (NV) and decreased blink response (BR).

Results :
As evidenced in Fig. 1, in the primary disease model, mice treated with DMM (n=10) had no differences in O, NV, and BR scores when compared with control mice (n=8) at all time periods. However, in the reactivation model, mice treated with DMM (n=4) displayed a pattern of reduced opacity and neovascularization when compared to their control counterparts (n=5) as seen in Fig. 2.

Conclusions : Our results are consistent with the hypothesis that disruption of oxidative phosphorylation via DMM would dampen the inflammatory response and minimize clinical symptoms of HSK. Interestingly, DMM did not have a significant effect on the clinical symptoms of primary HSV keratitis. Our understanding of the molecular mechanism of HSK is currently incomplete, and further studies will be necessary to elucidate what differences in the pathogenesis of primary HSV keratitis and HSK account for the differing clinical responses observed in this study.

This is a 2020 ARVO Annual Meeting abstract.

 

 

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