PURPOSE: Neuroprotectin D1 (NPD1) is an anti-inflammatory and proresolving lipid mediator biosynthesized from the omega-3-polyunsaturated fatty acid docosahexaenoic acid (DHA). The purpose of this study is to test the therapeutic potential of NPD1 for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK) using a mouse model. METHODS: C57BL/6 mice were infected ocularly with HSV-1 strain RE. Infected animals were treated topically with methyl ester prodrug NPD1 (300 ng/eye, 5-μL drop). Development of SK lesions, infiltration of inflammatory cells into the cornea, and production of proinflammatory cytokines, chemokines, and angiogenic factors were compared to untreated animals using slit-lamp biomicroscopy, flow cytometry, ELISA, and quantitative PCR (qPCR). RESULTS: Topical administration of NPD1 resulted in a significant reduction in the severity and incidence of SK, as well as the extent of corneal neovascularization in the NPD1-treated animals compared to their untreated counterparts. Infiltration of fewer neutrophils and pathogenic CD4⁺ T cells into the cornea, along with a lower number of cells that could be induced ex vivo to produce IFN-γ and IL-17, occurred with NPD1 treatment. Additionally, treatment with NPD1 diminished the production of proinflammatory cytokines, chemokines, and angiogenic factors, such as IL-6, CXCL1, CXCL-10, CCL-20, VEGF-A, MMP-2, and MMP-9 in the corneas of infected animals. Importantly, treatment with NPD1 increased the production of the anti-inflammatory cytokine, IL-10. CONCLUSIONS: Our novel findings demonstrate that NPD1 treatment could represent a valuable therapeutic approach to control SK lesions.
PURPOSE: Neuroprotectin D1 (NPD1) is an anti-inflammatory and proresolving lipid mediator biosynthesized from the omega-3-polyunsaturated fatty aciddocosahexaenoic acid (DHA). The purpose of this study is to test the therapeutic potential of NPD1 for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK) using a mouse model. METHODS: C57BL/6 mice were infected ocularly with HSV-1 strain RE. Infected animals were treated topically with methyl ester prodrug NPD1 (300 ng/eye, 5-μL drop). Development of SK lesions, infiltration of inflammatory cells into the cornea, and production of proinflammatory cytokines, chemokines, and angiogenic factors were compared to untreated animals using slit-lamp biomicroscopy, flow cytometry, ELISA, and quantitative PCR (qPCR). RESULTS: Topical administration of NPD1 resulted in a significant reduction in the severity and incidence of SK, as well as the extent of corneal neovascularization in the NPD1-treated animals compared to their untreated counterparts. Infiltration of fewer neutrophils and pathogenic CD4⁺ T cells into the cornea, along with a lower number of cells that could be induced ex vivo to produce IFN-γ and IL-17, occurred with NPD1 treatment. Additionally, treatment with NPD1 diminished the production of proinflammatory cytokines, chemokines, and angiogenic factors, such as IL-6, CXCL1, CXCL-10, CCL-20, VEGF-A, MMP-2, and MMP-9 in the corneas of infected animals. Importantly, treatment with NPD1 increased the production of the anti-inflammatory cytokine, IL-10. CONCLUSIONS: Our novel findings demonstrate that NPD1 treatment could represent a valuable therapeutic approach to control SK lesions.
Authors: Naveen K Rajasagi; Pradeep B J Reddy; Amol Suryawanshi; Sachin Mulik; Per Gjorstrup; Barry T Rouse Journal: J Immunol Date: 2010-12-27 Impact factor: 5.422
Authors: Bruce D Levy; Payal Kohli; Katherine Gotlinger; Oliver Haworth; Song Hong; Shamsah Kazani; Elliot Israel; Kathleen J Haley; Charles N Serhan Journal: J Immunol Date: 2007-01-01 Impact factor: 5.422
Authors: Kip M Connor; John Paul SanGiovanni; Chatarina Lofqvist; Christopher M Aderman; Jing Chen; Akiko Higuchi; Song Hong; Elke A Pravda; Sharon Majchrzak; Deborah Carper; Ann Hellstrom; Jing X Kang; Emily Y Chew; Norman Salem; Charles N Serhan; Lois E H Smith Journal: Nat Med Date: 2007-06-24 Impact factor: 53.440