Yang P, de Vos A F, Kijlstra A
Netherlands Ophthalmic Research Institute, Amsterdam, Netherlands.
Br J Ophthalmol. 1998 Jun;82(6):695-9. doi: 10.1136/bjo.82.6.695.
Previous studies have implied that interferon gamma (IFN-gamma) is involved in the pathogenesis of endotoxin induced uveitis (EIU) in the rat. This study investigated the source of IFN-gamma in the iris during EIU.
Whole mounts of iris were isolated from Lewis rats before and at different times (from 4 hours to 14 days) after foot pad injection of 200 micrograms Salmonella typhimurium lipopolysaccharide (LPS). Immunohistological analysis was performed using monoclonal antibodies (mAbs) specific to rat IFN-gamma (DB12 and DB13). mAbs specific to monocytes, macrophages, and dendritic cells and MHC class II were used to asses the inflammatory response in the eye (ED-1, ED-2, and OX-6). An antibody specific to neurofilaments (2H3) was used to stain nerve fibres in the normal iris.
LPS administration induced acute intraocular inflammation, characterised by a massive infiltration of monocytes/macrophages and increased numbers of MHC class II positive cells in the iris. IFN-gamma immunoreactive cells were not detected in iris whole mounts of control rats. Strikingly, IFN-gamma immunoreactivity was found in fibres from 4 hours until 10 days after LPS injection, with the most intense staining at 48-72 hours. Other DB12 or DB13 positive cells were not detected in the iris. The pattern of DB12 and DB13 staining in the inflamed iris was similar to the 2H3 staining of neurons in the iris of control rats.
These results show that systemic LPS administration induces IFN-gamma immunoreactivity in iris fibres and suggest that iris nerve fibres may be a source of IFN-gamma during EIU. The IFN-gamma immunoreactive material in the iris nerve fibres may be identical to neuronal IFN-gamma.
既往研究提示，γ干扰素（IFN-γ）参与大鼠内毒素诱导性葡萄膜炎（EIU）的发病机制。本研究调查了EIU期间虹膜中IFN-γ的来源。
从Lewis大鼠分离出虹膜全层，分别在足垫注射200微克鼠伤寒沙门氏菌脂多糖（LPS）之前以及注射后不同时间点（4小时至14天）进行处理。使用针对大鼠IFN-γ的单克隆抗体（mAb，DB12和DB13）进行免疫组织学分析。使用针对单核细胞、巨噬细胞、树突状细胞和MHC II类分子的mAb评估眼部的炎症反应（ED-1、ED-2和OX-6）。使用针对神经丝的抗体（2H3）对正常虹膜中的神经纤维进行染色。
给予LPS可诱导急性眼内炎症，其特征为单核细胞/巨噬细胞大量浸润以及虹膜中MHC II类阳性细胞数量增加。在对照大鼠的虹膜全层中未检测到IFN-γ免疫反应性细胞。令人惊讶的是，在LPS注射后4小时至10天的纤维中发现了IFN-γ免疫反应性，在48 - 72小时染色最强。在虹膜中未检测到其他DB12或DB13阳性细胞。炎症虹膜中DB12和DB13染色模式与对照大鼠虹膜中神经元的2H3染色相似。
这些结果表明，全身给予LPS可诱导虹膜纤维中的IFN-γ免疫反应性，并提示虹膜神经纤维可能是EIU期间IFN-γ的来源。虹膜神经纤维中的IFN-γ免疫反应性物质可能与神经元IFN-γ相同。
