Li T, Fox K, Fox A, Pakalnis V
Department of Microbiology & Immunology, University of South Carolina, School of Medicine, Columbia 29208.
Exp Eye Res. 1993 Jul;57(1):79-87. doi: 10.1006/exer.1993.1101.
The development of new therapeutic modalities in the treatment of uveitis has been greatly aided by the availability of suitable animal models. The endotoxin model excellently mimics many features of acute anterior uveitis. A new model that exhibits many features of recurrent anterior uveitis is described here. Muramyl dipeptide, MDP, is a synthetic monomer of Gram positive and Gram negative bacterial cell walls. The molecule is highly inflammatory, but unlike endotoxin does not elicit an antibody response. After a single injection (4 hr post-injection), acute anterior segment changes include massive engorgement of peri-limbal blood vessels, anterior chamber flare, fibrin deposits and heterophil (neutrophil) infiltration which subside within 24-48 hr. There is also break-down of the blood-aqueous barrier. With multiple injections the exacerbations and remissions continue to be observed after each injection but the disease progresses to a recurrent form including the development of synechiae and a mononuclear infiltrate into the anterior segment. The ocular changes are paralleled by changes in the bloodstream with recurrent heterophilia. Thus MDP does not elicit ocular or systemic tolerance. This new model of anterior uveitis should allow study of many of the events that occur in recurrent uveitis in man.
合适动物模型的可得性极大地促进了葡萄膜炎治疗新方法的发展。内毒素模型能出色地模拟急性前葡萄膜炎的许多特征。本文描述了一种展现复发性前葡萄膜炎诸多特征的新模型。胞壁酰二肽（MDP）是革兰氏阳性菌和革兰氏阴性菌细胞壁的合成单体。该分子具有高度炎症性，但与内毒素不同，它不会引发抗体反应。单次注射后（注射后4小时），眼前节急性变化包括角膜缘周围血管大量充血、前房闪辉、纤维蛋白沉积和嗜异性粒细胞（中性粒细胞）浸润，这些在24 - 48小时内消退。血 - 房水屏障也会遭到破坏。多次注射后，每次注射后都会持续观察到病情的加重和缓解，但疾病会发展为复发性形式，包括虹膜粘连的形成以及前节单核细胞浸润。眼部变化与血流中反复出现的嗜异性粒细胞增多相伴。因此，MDP不会引发眼部或全身耐受性。这种新的前葡萄膜炎模型应有助于研究人类复发性葡萄膜炎中发生的许多事件。
