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Toll-like receptor 4 and CD14 expression in human ciliary body and TLR-4 in human iris endothelial cells

Beatriz E Brito1, David O Zamora, Robert A Bonnah

  • 1Cellular and Molecular Pathology Laboratory, Experimental Medicine Center, Venezuelan Institute for Scientific Research (IVIC), Apdo 21827, Caracas 1020-A, Venezuela. bbrito@medicina.ivic.ve

Experimental Eye Research
|August 25, 2004
PubMed

Insights

Human eyes express endotoxin receptors Toll-like receptor-4 (TLR4) and CD14, particularly in the ciliary body. This finding explains the eye

Area of Science:

  • Ophthalmology
  • Immunology
  • Cell Biology

Background:

  • Endotoxin receptors, Toll-like receptor-4 (TLR4) and CD14, play crucial roles in innate immunity.
  • The presence and function of these receptors in ocular tissues, beyond the cornea, are not well-established.
  • Understanding ocular endotoxin receptor expression is vital for comprehending inflammatory responses in the eye.

Purpose of the Study:

  • To investigate the expression of TLR4 and CD14 proteins and mRNAs in human ocular tissues.
  • To determine the role of TLR4 in lipopolysaccharide (LPS)-induced inflammatory mediator secretion in the ciliary body.
  • To elucidate the potential interaction between TLR4 and CD14 in the anterior uveal tract.

Main Methods:

  • Immunohistochemical analysis of human eye sections using monoclonal antibodies against TLR4 and CD14.
  • Functional assays involving neutralizing anti-TLR4 antibodies to assess LPS-stimulated cytokine secretion.
  • Reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA expression of TLR4 and inflammatory cytokines in cultured iris microvascular endothelial cells.

Main Results:

  • Strong expression of TLR4 and CD14 proteins was detected in human ciliary body non-pigmented epithelial cells.
  • Neutralizing anti-TLR4 antibodies significantly inhibited LPS-stimulated tumor necrosis factor (TNF) secretion by the ciliary body.
  • TLR4 mRNA was constitutively expressed in iris endothelial cells, while LPS upregulated TNF-alpha, IL-1beta, IL-6, and IL-8 mRNA levels.

Conclusions:

  • This study provides the first evidence of intraocular TLR4 expression in the ciliary body and iris.
  • The co-localization of TLR4 and CD14 in the ciliary body suggests a functional interaction in endotoxin activation.
  • These findings help explain the susceptibility of the iris/ciliary body to bacterial endotoxin and its role in endotoxin-induced uveitis.

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