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N. K. Rajasagi, P. B. J. Reddy, A. Suryawanshi, P. Gjorstrup, B. T. Rouse; Application of Resolvin E1 Modulates the Severity of HSV-Induced Corneal Immunopathology. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3867.
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Resolvin E1, an endogenously produced lipid mediator derived from eicosapentaenoic acid has been shown to possess potent anti-inflammatory and pro-resolving properties. The purpose of this study is to assess the therapeutic potential of RvE1 for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK), a severe immunopathological disease of the eye.
Balb/c mice were ocularly infected with HSV-1 strain RE. Resolvin E1 (500 ng per eye; 5µl drop from 100µg/mL solution) was topically applied to the cornea two times daily starting from day1 until day 10 post infection. The eyes were examined on different days postinfection (dpi) with a slit-lamp biomicroscope (Kowa), and the clinical severity of stromal keratitis and angiogenesis of individually scored mice were recorded. Mice were sacrificed on day15pi and the infiltration of inflammatory cells into the corneas and production of pro-inflammatory cytokines were compared with untreated animals using flow cytometry and ELISA.
Topical administration of RvE1 resulted in a significant reduction in the severity and incidence of SK (p≤0.004) as well as the extent of corneal neovascularization (p≤0.009) in the treated animals compared to their untreated counterparts at day14dpi. We observed that treatment with RvE1 reduced the infiltration of neutrophils and pathogenic CD4+ T cells into the cornea, along with fewer numbers of CD4+ T cells that could be induced ex vivo to produce IFN-γ, IL-2 and IL-17. These cells are considered to be the primary orchestrators of the lesions. Additionally, treatment with RvE1 diminished the production of pro-inflammatory cytokines such as IL-6, IFN-γ and IL-17 in the corneas of infected animals. Interestingly, treatment with RvE1 increased the production of the anti-inflammatory cytokine, IL-10.
Taken together, these results show that treatment with Resolvin E1 significantly reduced the infiltration of leukocytes into the infected corneas and reduced the severity of SK lesions and neovascularization. Thus, our results indicate that RvE1 treatment may represent a useful approach in controlling lesion severity in virally induced immunopathological diseases.
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