Abstract
Abstract: :
Purpose: There is substantial clinical and experimental evidence implicating the role of gram–negative bacterial triggers in the pathogenesis of acute anterior uveitis (AAU), particularly those that are associated with HLA–B27. Toll–like receptor 4 (TLR4) is the primary signaling receptor for lipopolysaccharide (LPS) of gram–negative bacteria. The aim of the present study was to investigate the in vivo expression of TLR4 and its associated LPS receptor complex in the human eye. Methods: Normal human ocular tissues were evaluated for in vivo TLR4, MD–2, and CD14 mRNA and protein expression using RT–PCR and immunohistochemistry, respectively. The distribution patterns and phenotypes of the cells expressing these proteins were further characterized by confocal microscopy and double–label immunofluorescence studies. Results: Normal human uvea, retina, sclera, and conjunctiva constitutively expressed TLR4, MD–2, and CD14 mRNA. Resident antigen presenting cells (APCs) in the normal human uvea, consisting mainly of HLA–DR+ dendritic cells (DCs), expressed TLR4, MD–2, and CD14 protein in vivo. These APCs endowed with the complete LPS receptor complex appeared to be strategically positioned in perivascular and subepithelial locations for surveying blood–borne or intraocular LPS. On the other hand, other cell types of the normal human uvea, cornea, conjunctiva, retina, and sclera did not express TLR4/MD–2 protein in vivo as detectable by immunohistochemistry. Conclusions: The present study demonstrates for the first time that resident APCs in the normal human uvea express TLR4 and its associated LPS receptor complex. This has significant implications for our understanding of normal ocular immunity as well as unraveling the potential role of gram–negative bacteria in the pathogenesis of AAU.
Keywords: antigen presentation/processing • uvea • immunomodulation/immunoregulation