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Neutralization of Ocular Surface TNF-α Reduces Ocular Surface and Lacrimal Gland Inflammation Induced by In Vivo Dry Eye

Authors
 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 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.54(12) : 7557-7566, 2013 
Journal Title
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 
ISSN
 0146-0404 
Issue Date
2013
MeSH
Animals ; Cell Count ; Cornea/metabolism ; Cytokines/metabolism ; Dacryocystitis/drug therapy* ; Dacryocystitis/etiology ; Dacryocystitis/metabolism ; Disease Models, Animal* ; Enzyme-Linked Immunosorbent Assay ; Etanercept ; Female ; Goblet Cells/pathology ; Immunoglobulin G/pharmacology ; Keratitis/drug therapy* ; Keratitis/etiology ; Keratitis/metabolism ; Keratoconjunctivitis Sicca/complications* ; Lacrimal Apparatus/metabolism ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type I/pharmacology* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors*
Keywords
cytokines ; dry eye ; lacrimal gland ; tumor necrosis factor‐α
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Full Text
http://www.iovs.org/content/54/12/7557.long
DOI
10.1167/iovs.12-11515
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Hae Mi(노혜미)
Byun, Yu Jeong(변유정)
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Jeong, Eun Ae(정은애)
Choi, Wungrak(최웅락) ORCID logo https://orcid.org/0000-0002-3015-2502
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88852
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