Tikhonovich Marina V, Erdiakov Aleksei K, Gavrilova Svetlana A
Faculty of Medicine, M. V. Lomonosov Moscow State University, 27/1 Lomonosov Ave., Moscow, Russia, 119192.
Int Ophthalmol. 2018 Aug;38(4):1365-1378. doi: 10.1007/s10792-017-0594-3. Epub 2017 Jun 21.
This study proves the possibility of targeted use of the nonsteroidal anti-inflammatory drug lornoxicam to prevent the development of proliferative vitreoretinopathy (PVR). Triamcinolone acetonide (TA) was selected as a reference substance.
Wistar rats (N = 400) were used. PVR was modeled by intravitreal injection of dispase or concanavalin A. Lornoxicam or TA intravitreal administration was performed 20 min later. On the second and the third day, drugs were administrated systemic. Enucleation was performed on the first, third, seventh and 42nd or 56th day of the experiment.
Pro-inflammatory substances led to the development of sub- and epiretinal membranes. Lornoxicam decreased the incidence of membrane formation by 43 and 31% in dispase and concanavalin models, respectively. Membranes, formed during its use, were smaller and contained less fibrotic components. At the end of the experiment, the thickness of retinal and choroidal layers among the animals which had received the therapy was the same as the thickness of the retina and choroid of intact rats. Lornoxicam administration normalized the cyclooxygenases (COXs) expression in the retina and the choroid at the early stages of the experiment. TA application was less effective in both models.
COXs blocking during the development of PVR, overwhelming inflammation in the eye and reducing its consequences, is proved to be a much more effective and safe influence than the suppression of the entire cascade of arachidonic acid metabolism. Lornoxicam did not only improve the condition of the retina and the choroid but also significantly reduced the frequency of membrane formation.
本研究证实了靶向使用非甾体抗炎药氯诺昔康预防增殖性玻璃体视网膜病变（PVR）发展的可能性。选择曲安奈德（TA）作为对照物质。
使用Wistar大鼠（N = 400）。通过玻璃体内注射Dispase或伴刀豆球蛋白A建立PVR模型。20分钟后进行氯诺昔康或TA玻璃体内给药。在第二天和第三天进行全身给药。在实验的第一天、第三天、第七天以及第42天或第56天进行眼球摘除。
促炎物质导致视网膜下和视网膜前膜的形成。在Dispase和伴刀豆球蛋白模型中，氯诺昔康分别使膜形成的发生率降低了43%和31%。在使用氯诺昔康过程中形成的膜较小，且纤维化成分较少。在实验结束时，接受治疗的动物的视网膜和脉络膜层厚度与正常大鼠的视网膜和脉络膜厚度相同。在实验早期，氯诺昔康给药使视网膜和脉络膜中的环氧化酶（COXs）表达正常化。在两个模型中，TA的应用效果较差。
事实证明，在PVR发展过程中阻断COXs、控制眼内炎症并减轻其后果，比抑制整个花生四烯酸代谢级联反应更有效且更安全。氯诺昔康不仅改善了视网膜和脉络膜的状况，还显著降低了膜形成的频率。
