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Y. Sato, T. Watanabe, H. Keino, A. Kudo, H. Kawakami, A. A. Okada; High Mobility Group Box Protein-1 in Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):827.
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To investigate whether high mobility group box protein-1 (HMGB-1), acting as a novel proinflammatory cytokine, is involved in experimental autoimmune uveoretinitis (EAU).
HMGB-1 concentration was measured in aqueous humor and serum obtained from Lewis rats immunized with interphotoreceptor retinoid binding protein (IRBP) peptide (R14) and complete Freund’s adjuvant (CFA), rats immunized with CFA, and non-treated rats on day 14 after immunization. Immunofluorescence histochemistry was performed to examine localization of HMGB-1 and the receptor for advanced glycation end products (RAGE) in eyes obtained from non-treated rats or EAU-induced rats.
The level of HMGB-1 in aqueous humor was significantly elevated in eyes with EAU, and both HMGB-1 and TNF- levels correlated with active ocular inflammation. HMGB-1 was expressed in the iris, ciliary body and retina of eyes from non-treated rats and EAU-induced rats. Furthermore, HMGB-1 and RAGE were found in inflammatory cells infiltrating into the anterior chamber, vitreous cavity, and subretinal space in EAU-induced rats. Some HMGB-1 or RAGE positive cells in eyes with EAU were CD68 positive.
HMGB-1 was found to be elevated in the aqueous humor of eyes with EAU. Inflammatory cells infiltrating ocular tissues expressed both HMGB-1 and RAGE. These results support the possibility that extracellularly-released HMGB-1 acts as a novel proinflammatory cytokine to promote and amplify ocular inflammation in autoimmune uveoretinitis.
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