Arroul-Lammali A, Djeraba Z, Belkhelfa M, Belguendouz H, Hartani D, Lahlou-Boukoffa O S, Touil-Boukoffa C
Équipe cytokines et NO synthases/immunité et pathogénie, laboratoire de biologie cellulaire et moléculaire (LBCM), faculté des sciences biologiques, USTHB, BP 32, El Alia, 16111 Alger, Algeria.
J Fr Ophtalmol. 2012 Apr;35(4):251-9. doi: 10.1016/j.jfo.2011.05.003. Epub 2011 Oct 19.
Autoimmune uveitis is a group of HLA-associated inflammatory diseases of the eye, prevalent worldwide, that may cause blindness. It can be limited to the eye, or associated with a systemic syndrome. Furthermore, patients suffering from uveitis exhibit high serum and local nitric oxide (NO) levels as a consequence of cellular responses to immunologically privileged antigens within the eye such as interphotoreceptor retinoid binding protein (IRBP). To investigate NO production kinetics in autoimmune uveitis and its implication in mechanisms of ocular pathogenesis, we first attempted to develop an experimental model of autoimmune uveitis (EAU) on the Wistar rat, using the whole bovine retinal interphotoreceptor matrix extract (IPMe) and isolated IRBP.
Female Wistar rats (n=24) were divided into three experimental groups: "control rats" (n=3) consisting of non-immunized animals, "IRBP-immunized rats" (n=12) and "IPMe-immunized rats" (n=9), which received a subcutaneous injection, respectively, of 13 μg IRBP and 100 μg IPMe emulsified in complete Freund's adjuvant. On days 7, 14 and 21 post immunization, the rats were sacrificed. Nitrites were assessed in plasma and in homogenate of eyes using the Griess reaction. Meanwhile, eyes were collected for histological studies.
Our results show the sensitivity of the Wistar strain to both IPMe and IRBP-induced EAU. In fact, we observed histological disorders affecting the retinal tissue in both models of EAU. On the other hand, a significantly increased production of NO in plasma and homogenate of eyes was also observed in comparison to the control group. Moreover, we noted with interest that maximal production of NO occurs prior to the alteration of retinal tissue.
In summary, our results suggest the early involvement of NO in the mechanisms of pathogenesis of EAU. NO can be considered as a key bio-marker of poor prognosis in ocular autoimmune inflammation.
自身免疫性葡萄膜炎是一组与 HLA 相关的眼部炎症性疾病，在全球范围内普遍存在，可能导致失明。它可以局限于眼部，也可与全身综合征相关。此外，由于眼部对免疫豁免抗原（如光感受器间维生素 A 结合蛋白（IRBP））的细胞反应，葡萄膜炎患者的血清和局部一氧化氮（NO）水平较高。为了研究自身免疫性葡萄膜炎中 NO 的产生动力学及其在眼部发病机制中的作用，我们首先尝试在 Wistar 大鼠上建立自身免疫性葡萄膜炎（EAU）的实验模型，使用全牛视网膜光感受器间基质提取物（IPMe）和分离的 IRBP。
将 24 只雌性 Wistar 大鼠分为三个实验组：“对照大鼠”（n = 3），由未免疫的动物组成；“IRBP 免疫大鼠”（n = 12）和“IPMe 免疫大鼠”（n = 9）分别皮下注射乳化于完全弗氏佐剂中的 13 μg IRBP 和 100 μg IPMe。在免疫后第 7、14 和 21 天，处死大鼠。使用 Griess 反应评估血浆和眼匀浆中的亚硝酸盐。同时，收集眼睛进行组织学研究。
我们的结果显示 Wistar 品系对 IPMe 和 IRBP 诱导的 EAU 均敏感。事实上，我们在两种 EAU 模型中均观察到影响视网膜组织的组织学紊乱。另一方面，与对照组相比，血浆和眼匀浆中 NO 的产生也显著增加。此外，我们有趣地注意到，NO 的最大产生发生在视网膜组织改变之前。
总之，我们的结果表明 NO 在 EAU 发病机制中早期参与。NO 可被视为眼部自身免疫性炎症预后不良的关键生物标志物。
