Jacquemin E, de Kozak Y, Thillaye B, Courtois Y, Goureau O
Laboratoire de Développment, Vieillissement et Pathologie de la Rétine, Paris, France.
Invest Ophthalmol Vis Sci. 1996 May;37(6):1187-96.
Inducible nitric oxide (NO) synthase (iNOS) has been implicated in the pathogenesis of endotoxin-induced uveitis (EIU). This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat.
EIU was induced in Lewis rats by a single foot pad injection of 150 micrograms lipopolysaccharide (LPS) from Salmonella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS localization by in situ hybridization, and comparison of OX-42- and ED1-positive cell appearance and of glial response by specific immunohistochemistry.
iNOS mRNA was not detected in the iris-ciliary body nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in stromal cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours after LPS injection. iNOS-positive cells were also present on the vitreous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- and ED1-positive cells (microglia, macrophages, or polymorphonuclear leukocytes) colocalized in part with some iNOS-positive cells in the ciliary body and in the retina. Furthermore, expression of iNOS in Müller cells cannot be excluded.
These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA expression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the eye and the retina are the major source of NO. These results support the hypothesis that both inflammatory and resident ocular cells are involved in iNOS expression during EIU.
诱导型一氧化氮（NO）合酶（iNOS）与内毒素诱导的葡萄膜炎（EIU）的发病机制有关。本研究旨在确定大鼠EIU期间眼部表达iNOS的细胞。
通过向Lewis大鼠的单个足垫注射150微克鼠伤寒沙门氏菌脂多糖（LPS）诱导EIU。在LPS注射后的不同时间间隔，作者评估眼部炎症（裂隙灯观察），通过原位杂交确定iNOS定位，并通过特异性免疫组织化学比较OX-42和ED1阳性细胞的出现情况以及神经胶质反应。
在对照大鼠的虹膜睫状体和视网膜中未检测到iNOS mRNA。LPS注射后6小时，在虹膜睫状体的上皮细胞中强烈检测到iNOS mRNA，16小时后在睫状突的基质细胞中也检测到。在神经视网膜中，LPS注射后16小时在内层观察到iNOS mRNA。此时玻璃体上也存在iNOS阳性细胞。LPS注射后6小时和大约16小时，免疫组织化学实验显示大量OX-42和ED1阳性细胞（小胶质细胞、巨噬细胞或多形核白细胞）部分与睫状体和视网膜中的一些iNOS阳性细胞共定位。此外，不能排除Müller细胞中iNOS的表达。
这些观察结果证实皮下注射内毒素可显著诱导眼部NOS mRNA表达，并表明虹膜睫状体的上皮细胞以及浸润眼前段和视网膜的细胞是NO的主要来源。这些结果支持炎症细胞和眼部常驻细胞均参与EIU期间iNOS表达的假说。
