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Pawan Kumar Singh, Ajay Kumar, Ashok Kumar; Resolvin D1 (RvD1) promotes the resolution of inflammation and protects mice from S. aureus endophthalmitis via Toll-Like Receptor 2 signaling.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3575. doi: https://doi.org/.
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Acute inflammation plays an important role in protecting the host tissue from damage. However, unless inflammation is resolved in a timely manner, irreversible damage and even blindness may result in cases of bacterial endophthalmitis. Here, we investigated the potential therapeutic use of a bioactive lipid, Resolvin D1 (RvD1), in a mouse model of S. aureus endophthalmitis. Furthermore, we assessed the role of TLR2 signaling in the RvD1-mediated anti-inflammatory process.
Endophthalmitis was induced in wild type (WT), C57BL/6, and TLR2-/- mice via intravitreal injections of S. aureus. Both the prophylactic and therapeutic effects of RvD1 were assessed by treating the eyes either before (12h) or after (6h and 12h) bacterial infection, respectively. The progression of disease was monitored via ophthalmoscopic, electroretinography (ERG), histological, cell death (TUNEL labeling), and microbiological parameters. The expression of cytokines and chemokines was assessed by qRT-PCR and ELISA. Flowcytometry was used to determine cellular infiltration.
Intravitreal injections of RvD1 in the eyes of WT, but not TLR2-/-, mice both prior to and after S. aureus infection, significantly improved the outcome of the disease. RvD1-treated eyes of the WT mice exhibited significantly reduced levels of pro-inflammatory cytokines and chemokines (IL-1β, IL6, TNF-α, MIP2, and KC). Similarly, both the bacterial burden and the level of infiltrating PMNs were reduced in the treatment groups. Interestingly, RvD1 treatment resulted in the induced expression of several anti-inflammatory (IL-4, IL-10, and TGF-β) and anti-microbial (S100A7, S100A8, S100A9, MMP2, MMP9, and MMP13) molecules in the WT mice. In contrast, RvD1 treatment has no effect on either pro-inflammatory or anti-inflammatory mediators in TLR2-/- mice.
Our study demonstrates, for the first time, that RvD1 has potent anti-inflammatory effects in bacterial endophthalmitis and actively promotes the resolution of inflammation. Furthermore, the failure of RvD1 to induce protection in TLR2-/- mice suggests the potential involvement of TLR2-signaling in regulating bioactive lipid activity in the eye.
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