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Naveen K Rajasagi, Barry T Rouse; Aspirin-triggered Resolvin D1 reduces the severity of HSV-induced corneal immunopathology. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1850.
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The purpose of this study is to evaluate the therapeutic potential of Aspirin-triggered Resolvin D1 (AT-RvD1) for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK), an immunopathological disease of the eye.
Balb/c mice were ocularly infected with HSV-1 strain RE. AT-RvD1 (100 ng per eye; 5µl drop) was topically applied to the cornea two times daily starting from day 6 until day 12 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, chemokines were compared with untreated animals using flow cytometry and quantitative PCR.<br /> <br />
Topical administration of AT-RvD1 resulted in a significant reduction in the severity and incidence of SK as well as the extent of corneal neovascularization in the treated animals compared to their untreated counterparts at day15dpi. We observed that treatment with AT-RvD1 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 AT-RvD1 diminished the production of pro-inflammatory cytokines and chemokines such as IL-6 and CXCL1 in the corneas of infected animals.
Taken together, these results show that treatment with AT-RvD1 significantly reduced the infiltration of leukocytes into the infected corneas and reduced the severity of SK lesions and neovascularization. Thus, our results indicate that AT-RvD1 treatment may represent a useful approach in controlling lesion severity in virally induced immunopathological diseases.<br />
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