Augmenting Endogenous Levels of Retinal Annexin A1 Suppresses Uveitis in Mice.
Augmenting Endogenous Levels of Retinal Annexin A1 Suppresses Uveitis in Mice.
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DOI：
10.1167/tvst.6.5.10
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发表时间：
2017-09
影响因子：
3
通讯作者：
Dick AD
中科院分区：
文献类型：
--
作者：
Gardner PJ;Yazid S;Ribeiro J;Ali RR;Dick AD
本研究的目的是检查抗炎蛋白膜联蛋白A1（AnxA 1）在葡萄膜炎期间小鼠和人视网膜中的表达，并确定局部施用人重组AnxA 1（hrAnxA 1）是否可以抑制小鼠葡萄膜炎。对来自小鼠（健康正常和葡萄膜炎）和死后人（无眼病史（n = 5）和葡萄膜炎史（n = 7））的视网膜切片进行AnxA 1表达染色，并通过免疫荧光显微镜成像。通过与CD 45、胶质细胞酸性蛋白（GFAP）和Iba-1细胞共标记，并对AnxA 1受体甲酰肽受体1（FPR 1）和FPRL 1/FPR 2进行额外染色，测定AnxA 1细胞表达。通过玻璃体内注射hrAnxA 1局部治疗患有急性内毒素诱导的葡萄膜炎和慢性实验性自身免疫性葡萄膜炎的小鼠，并通过临床评分和流式细胞术定量白细胞浸润来评估疾病。在健康小鼠和人类视网膜中均观察到AnxA 1的组成性表达，并且与健康对照相比，其表达在葡萄膜炎期间增加。AnxA 1主要与CD 45+细胞、GFAP+大胶质细胞共定位，并且在较小程度上与Iba-1+骨髓细胞共定位。我们还表明，局部治疗hrAnxA 1减弱小鼠葡萄膜炎的严重程度。这些数据表明，局部表达的AnxA 1在眼内炎症期间在视网膜中升高。我们证明，局部施用hrAnxA 1以增加水平导致小鼠葡萄膜炎的抑制。我们的数据表明，视网膜AnxA 1在人类葡萄膜炎的表达升高可能是免疫调节和局部补充hrAnxA 1可能提供一个潜在的新的治疗炎症性眼病，如非感染性葡萄膜炎。
The purpose of this study was to examine the expression of the anti-inflammatory protein Annexin A1 (AnxA1) in mice and human retinae during uveitis and to determine whether local administration of human recombinant AnxA1 (hrAnxA1) can suppress uveitis in mice. Retinal sections from mice (healthy normal and uveitis) and postmortem human (no history of eye disease (n = 5) and uveitis (n = 7)) were stained for AnxA1 expression and imaged by immunofluorescence microscopy. AnxA1 cellular expression was determined by colabeling with CD45, glial fibrillary acidic protein (GFAP), and Iba-1 cells, with additional staining of AnxA1 receptors formyl peptide receptor 1 (FPR1) and FPRL1/FPR2. Mice with acute endotoxin-induced uveitis and chronic experimental autoimmune uveitis were treated locally by intravitreal injection with hrAnxA1, and disease was assessed by clinical scoring and quantification of leukocyte infiltrate via flow cytometry. Constitutive expression of AnxA1 was observed in both healthy mouse and human retinae, and its expression increased during uveitis compared to healthy controls. AnxA1 colocalizes predominantly with CD45+ cells, GFAP+ macroglia, and to a lesser extent, Iba-1+ myeloid cells. We also demonstrate that local treatment with hrAnxA1 attenuates the severity of uveitis in mice. These data indicate that locally expressed AnxA1 is elevated in the retina during intraocular inflammation. We demonstrate that local administration of hrAnxA1 to augment levels results in suppression of uveitis in mice. Our data suggest that elevated expression of retinal AnxA1 in human uveitis may be immunoregulatory and that local supplementation with hrAnxA1 may provide a potential novel treatment for inflammatory eye diseases such as noninfectious uveitis.
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影响因子：
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影响因子：
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