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H. Xu, R. Dawson, J.V. Forrester, J. Liversidge; Juxtapapilliary and Retinal Margin Areas – Are They Immunological Weak Points? . Invest. Ophthalmol. Vis. Sci. 2005;46(13):991.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Induction of retinal inflammation by adoptively transfer of retinal antigen specific T cells implies local presentation of retinal antigens. However, the identity and properties of antigen–presenting cells (APCs) in the retina are not established. The current study was undertaken to identify potential APCs in mouse retina. Methods: Experimental autoimmune uveoretinitis (EAU) was induced in either C57BL/6 mice or B10R.III mice using IRBP peptide. Blood retinal–barrier (BRB) breakdown was evaluated by intravenously injection of Evan’s blue dye. Pre–activated calcein–AM labelled T lymphocytes were adoptively transferred into early stage EAU mice. Wholemount retinas of normal and EAU mice were stained for MHCII, CD1b, CD11c, F4/80, CD205, CD8α, DC marker (33D1), CD80 and CD86 and observed by confocal scanning laser microscopy Results: In normal non–immunized mice, MHC–II+ cells in the juxtapapillary and retinal margin areas were detected at two weeks post–natal. The number of MHC–II+ cells increased with age. The cells were CD11blow, 33D1high (DC maker) but negative for CD8α, CD205, CD11c, F4/80, CD80 and CD86. Ex vivo stimulation of retinal whole mounts with LPS showed no effect on expression of these molecules. All MHC–II+ cells displayed dendriform shape and some showed close perivascular contact. Most cells were located in the inner neuroretinal layer except in the optic disc area where some MHC–II+ cells were also located in deep retina. In mice with early retinal inflammation (EAU), the number of MHC–II+ 33D1+ cells increased and many more cells showed perivascular distribution. Early BRB breakdown was mainly located in the juxtapapillary and retinal margin areas and this was correlated with location of early T lymphocyte infiltration. Thus, the peripheral juxtapapillary retina were identified as two sites of initial retinal inflammation in both C57BL/6 and B10R.III mice. Conclusions: The predilection for initial inflammation at the retinal margin and juxtapapillary areas indicates that they are preferential sites for immunological attack compared to other retinal areas. Specific location of MHC–II+ 33D1+ cells in these areas in normal mice and increasing in numbers in early EAU mice suggest that these areas may represent sites of initial antigen presentation.
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