John H Chang1, Peter McCluskey, Denis Wakefield. 1. Laboratory of Ocular Immunology, Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia.
Abstract
PURPOSE: To investigate the in vivo expression of toll-like receptor 4 (TLR4) and its associated lipopolysaccharide (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 by 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. The protein expression of these molecules was restricted, however, to resident antigen-presenting cells (APCs) in the normal human uvea, consisting mainly of HLA-DR(+) dendritic cells (DCs). 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. In contrast, other cell types of the normal human 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 the understanding of normal ocular immunity as well as unraveling the potential role of Gram-negative bacteria in the pathogenesis of acute anterior uveitis (AAU).
PURPOSE: To investigate the in vivo expression of toll-like receptor 4 (TLR4) and its associated lipopolysaccharide (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 by 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. The protein expression of these molecules was restricted, however, to resident antigen-presenting cells (APCs) in the normal human uvea, consisting mainly of HLA-DR(+) dendritic cells (DCs). 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. In contrast, other cell types of the normal human 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 the understanding of normal ocular immunity as well as unraveling the potential role of Gram-negative bacteria in the pathogenesis of acute anterior uveitis (AAU).
Authors: S Rodríguez-Martínez; M E Cancino-Díaz; L Jiménez-Zamudio; E García-Latorre; J C Cancino-Díaz Journal: Br J Ophthalmol Date: 2005-07 Impact factor: 4.638
Authors: Alastair K Denniston; Paul Tomlins; Geraint P Williams; Sherine Kottoor; Imran Khan; Kadambari Oswal; Mike Salmon; Graham R Wallace; Saaeha Rauz; Philip I Murray; S John Curnow Journal: Invest Ophthalmol Vis Sci Date: 2012-02-21 Impact factor: 4.799