December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Functional Roles for TLR4, TNF- and IL-1 in a Murine Model of Endotoxin Induced Keratitis
Author Affiliations & Notes
  • VY Lin
    Ophthalmology Case Western Reserve University Cleveland OH
  • ME Pennini
    Cleveland OH
  • RB Berger
    Cleveland OH
  • FO Gulden
    Cleveland OH
  • JH Lass
    Cleveland OH
  • E Diaconu
    Cleveland OH
  • E Pearlman
    Cleveland OH
  • Footnotes
    Commercial Relationships   V.Y. Lin, None; M.E. Pennini , None; R.B. Berger , None; F.O. Gulden , None; J.H. Lass , None; E. Diaconu , None; E. Pearlman , None. Grant Identification: NIH grants RO1EY10320, P30EY11373 and the Research to Prevent Blindness Foundation
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2261. doi:
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      VY Lin, ME Pennini, RB Berger, FO Gulden, JH Lass, E Diaconu, E Pearlman; Functional Roles for TLR4, TNF- and IL-1 in a Murine Model of Endotoxin Induced Keratitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2261.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: Bacterial endotoxin, lipopolysaccharide (LPS), is a potent stimulator of inflammatory response, and contributes to microbial keratitis and to the pathogenesis of sterile corneal ulcers. Previous studies using this mouse model showed that LPS-induced stromal abnormalities are due to neutrophil infiltration to the cornea and require Toll-like receptor (TLR)-4 signaling. In this study, we determined the relative contributions of IL-1α, which signals through the same intracellular pathway as TLR4, and of another pro-inflammatory cytokine TNF-α, in development of endotoxin-induced keratitis. Methods: Corneas of LPS responsive C3H/HeN mice and congenic C3H/HeJ mice were abraded. 10 ug of Pseudomonas aeruginosa endotoxin was applied to the corneal surface. Antibody to TNF-α or IL-1α was injected into the subconjunctival space, and stromal thickness and stromal haze were measured after 24h using Confocal Microscopy Through Focusing. Neutrophil infiltration was determined by immunohistochemistry. Results: Stromal thickness and haze were significantly elevated in endotoxin treated C3H/HeN mice compared with corneas exposed to water, and compared with endotoxin-treated C3H/HeJ mice (which have a mutation in TLR4). Stromal thickness and stromal haze in endotoxin treated C3H/HeN mice given either anti-TNF-α or anti-IL-1α was significantly reduced compared with control mice injected with normal rat IgG. Neutrophil infiltration to the corneal stroma was also significantly reduced in anti-TNF-α and anti-IL-1α treated mice. Conclusion: In addition to TLR4, IL-1α and TNF-α are essential for development of endotoxin-induced keratitis.

Keywords: 449 keratitis • 380 cytokines/chemokines • 469 microbial pathogenesis: experimental studies 

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