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Yongwoo Ji, Yu Jeong Byun, Jin Sun Kim, Eunae Jeong, Hyung Keun Lee; Neutralization of Ocular Surface TNF-α Reduces Ocular Surface and Lacrimal Gland Inflammation Induced by In Vivo Dry Eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):910.
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© ARVO (1962-2015); The Authors (2016-present)
The purposes of this study are to investigate the effectiveness of tumor necrosis factor (TNF)-α blocker for treatment of dry eye (DE)-induced inflammation and determine a more effective method to suppress lacrimal gland inflammation. Efficacy of topical vs. systemic administration of TNF-α blockers was determined using a murine DE model.
The TNF-α blocker HL036 was developed by modification of the TNF receptor I. Protein purity, binding affinity, and clearance of TNF-α was compared with etanercept. Using DE induced C57BL/6 mice, corneal erosion, tear secretion, and goblet cell counts were measured after subcutaneous or topical treatment with etanercept or HL036. Inflammatory cytokines in cornea and lacrimal glands were determined by quantitative reverse transcription polymerase chain reaction and enzyme-linked immune absorbent assay.
HL036 showed TNF-α binding affinity comparable to etanercept, as measured by surface plasmon resonance. HL036 concentration was significantly higher in cornea and anterior segment than etanercept, and effectively eliminated TNF-α on ocular surfaces. Etanercept was preferentially concentrated in the posterior segment. Corneal erosion, goblet cell counts, and tear secretion were improved only with topically applied etanercept and HL036. Ocular surface interferon-γ (IFN-γ), interleukin-6 (IL-6), IL-21, and IL-22 were significantly decreased by topical HL036. DE induced lacrimal gland IFN-γ and IL-6 expression was effectively suppressed by topical etanercept, glucocorticoid, and HL036.
Topical TNF-α blockers effectively suppressed lacrimal gland and corneal inflammation by suppressing IFN-γ, IL-21, and IL-6. Differences in TNF-α affinity, clearance, and local concentration of blockers may account for the anti-inflammatory effects in different ocular regions.
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