Purchase this article with an account.
Yong Woo Ji, Yu Jeong Byun, Wungrak Choi, Eunae Jeong, Jin Sun Kim, Haemi Noh, Eun Sun Kim, Yun Jung Song, Seung Kook Park, 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(12):7557-7566. doi: 10.1167/iovs.12-11515.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was 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 versus systemic administration of TNF-α blockers was determined using a murine dry eye (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 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 RT-PCR and ELISA.
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 and goblet cell counts were improved only with topically applied etanercept and HL036. Ocular surface IFN-γ, IL-6, and IL-21 were significantly decreased by topical HL036. DE-induced lacrimal gland IFN-γ and IL-6 expression was effectively suppressed by topical etanercept 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.
This PDF is available to Subscribers Only