Abstract | PURPOSE: METHODS: LPS was injected intrastromally into the corneas of C57BL/6 mice followed by treatment with a solution of 2.5% EP in 0.2% hydroxypropyl methylcellulose (HPMC) every 90 minutes during the course of 12 hours. Prednisolone acetate 1% solution ( PRED FORTE) was used as a positive control. Mice were sacrificed after 3 days, and corneas were examined by in vivo confocal microscopy and analyzed for infiltrated cells by flow cytometry. Gr-1, TNF-α, and pNF-κB-p65 were detected immunohistochemically, and TNF-α, IL-6, and IL-1β levels were quantified by ELISA. RESULTS: LPS-induced haze in mice corneas was decreased by 2-fold upon EP treatment; however, it was not changed upon PRED FORTE treatment. Flow cytometry and immunohistochemistry showed infiltration of leukocytes in the LPS-treated corneas; among the infiltrated cells, neutrophils (Gr-1+ and CD11b+) and macrophages (F4/80+ and CD11b+) were 3403.4- and 4.5-fold higher in number, respectively, than in vehicle-treated control corneas. EP or PRED FORTE treatment of LPS-injected corneas decreased the number of neutrophils 7.5- and 7.2-fold and macrophages by 5.6- and 3.5-fold, respectively. Both EP and PRED FORTE decreased TNF-α and IL-6 expression considerably, and to a lesser extent IL-1β expression, in the LPS-treated corneas. CONCLUSIONS: The present study demonstrated that EP reduces LPS-induced inflammation in the cornea and thus may have a potential therapeutic application in the inhibition of corneal inflammation.
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Authors | Divya Gupta, Yiqin Du, Jordan Piluek, Adam M Jakub, Kristine Ann Buela, Akshar Abbott, Joel S Schuman, Nirmala SundarRaj |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 53
Issue 10
Pg. 6589-99
(Sep 25 2012)
ISSN: 1552-5783 [Electronic] United States |
PMID | 22918642
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Gr-1 protein, mouse
- Lipopolysaccharides
- Ophthalmic Solutions
- Pyruvates
- Receptors, Chemokine
- Transcription Factor RelA
- Tumor Necrosis Factor-alpha
- ethyl pyruvate
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Topics |
- Animals
- Anti-Inflammatory Agents
(therapeutic use)
- Cell Migration Assays, Leukocyte
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Flow Cytometry
- Fluorescent Antibody Technique, Indirect
- Keratitis
(chemically induced, metabolism, prevention & control)
- Leukocytes
(physiology)
- Lipopolysaccharides
(toxicity)
- Mice
- Mice, Inbred C57BL
- Microscopy, Confocal
- Ophthalmic Solutions
(therapeutic use)
- Pyruvates
(therapeutic use)
- Receptors, Chemokine
(metabolism)
- Transcription Factor RelA
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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