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Updated: Aug 23, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
Influence of dimethylfumarate on experimental HSV-1 necrotizing keratitis
A Heiligenhaus1, H Li, S Wasmuth
1Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Hohenzollernring 74, 48145 Muenster, Germany. arnd.heiligenhaus@uveitis-zentrum.de
Background:
This study was performed to investigate the influence of fumaric acid esters on the course of herpes stromal keratitis (HSK).
Methods:
The corneas of BALB/c mice were inoculated with 105 plaque-forming units of herpes simplex virus 1 (HSV-1, KOS strain). Groups of mice were treated intraperitoneally with phosphate buffered saline (PBS) (control mice), or with dimethylfumarate (DMF) at 15 mg/kg of body weight dissolved in PBS daily for 28 days pre-infection and for 14 days post-infection. The course of HSV-1 keratitis was studied clinically. Corneal sections were examined for inflammatory cell infiltration. The numbers of CD3, GR-1, CD11b and F4/80-expressing cells infiltrating the corneas were analyzed by immunohistochemistry.
Results:
On day 14 after HSV infection, 72% of the mice in the control group had severe HSK. The development of HSK was reduced by DMF treatment in the DMF group (22%) (P=0.004). The total number of inflammatory cells and infiltration of polymorphonuclear-neutrophils (PMNs) were reduced in the corneas of DMF-treated mice. Compared to the PBS-treated mice, numbers of CD3, CD11b, GR-1 and F4/80-positive cells were reduced in the DMF group of mice.
Conclusions:
The course of experimental herpes stromal keratitis can be improved with systemic fumaric acid ester treatment. The improvement of keratitis correlates with a reduced corneal infiltration of T cells and mononuclear cells.
Insights
Systemic fumaric acid ester treatment, specifically dimethylfumarate (DMF), significantly reduced herpes stromal keratitis (HSK) in mice. This treatment decreased inflammatory cell infiltration in the cornea, improving the overall course of experimental HSK.
Area of Science:
- Ophthalmology
- Immunology
- Virology
Background:
- Herpes simplex virus type 1 (HSV-1) can cause herpes stromal keratitis (HSK), a significant cause of vision loss.
- Investigating therapeutic interventions for HSK is crucial for preventing corneal damage and vision impairment.
Purpose of the Study:
- To evaluate the efficacy of fumaric acid esters, specifically dimethylfumarate (DMF), in treating experimental herpes stromal keratitis (HSK).
Main Methods:
- BALB/c mice were infected with HSV-1 and treated with dimethylfumarate (DMF) or phosphate-buffered saline (PBS).
- Clinical assessment of keratitis and immunohistochemical analysis of corneal inflammatory cell infiltration (CD3, GR-1, CD11b, F4/80) were performed.
Main Results:
- DMF treatment significantly reduced the incidence and severity of HSK compared to the control group (22% vs. 72%).
- DMF administration led to a marked decrease in the infiltration of total inflammatory cells, polymorphonuclear-neutrophils (PMNs), T cells, and mononuclear cells in the cornea.
Conclusions:
- Systemic administration of fumaric acid esters (DMF) effectively ameliorates experimental herpes stromal keratitis.
- The therapeutic benefit of DMF in HSK is associated with reduced corneal infiltration of immune cells, including T cells and mononuclear cells.
