Hu Wenzheng, Criswell Mark H, Ottlecz Anna, Cornell Tammy L, Danis Ronald P, Lambrou George N, Ciulla Thomas A
Retina Service Research Laboratories, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Retina. 2005 Dec;25(8):1054-64. doi: 10.1097/00006982-200512000-00015.
To determine whether lumiracoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that exhibits anti-inflammatory and antiangiogenic properties, can inhibit experimental choroidal neovascular membrane (CNVM) development induced by focal laser trauma in a well-characterized Brown Norway rat CNVM model.
Over a 35-day period, 24 rats received daily oral gavage dosages of 20 mg/kg lumiracoxib in a 0.5% (w/v) suspension of sodium carboxymethylcellulose (CMC), while a control group received the 0.5% CMC suspension only. After 7 days, eight laser photocoagulation sites were placed concentrically around the optic disk to induce CNVMs. Thirty-five days later, fundus photography and fluorescein angiography (FA) were performed and eyes were processed for histopathologic analysis.
Masked FA grading of lesion sites revealed a small, but statistically significant difference (P<0.0001) in late stage staining intensity and leakage between the mean group scores of treated (1.4) and control (1.7) eyes. Histopathologic analysis demonstrated that the mean CNVM thickness +/- SD of 38 +/-19 microm (n=24 eyes, 175 photocoagulation sites) in the lumiracoxib-treated animals was reduced by 30% (P<0.001) compared to the CNVM mean thickness+/- SD of 54+/- 20 microm (n=24 eyes, 171 photocoagulation sites) in the control animals.
Systemic administration of the selective COX-2 inhibitor lumiracoxib results in a partial but significant reduction in CNVM development in the rat laser-trauma model and thus may be clinically beneficial as a potential inhibitor of CNVM formation in exudative age-related macular degeneration.
确定鲁米昔布(一种具有抗炎和抗血管生成特性的高选择性环氧化酶-2(COX-2)抑制剂)是否能在特征明确的棕色挪威大鼠脉络膜新生血管膜(CNVM)模型中抑制局灶性激光损伤诱导的实验性脉络膜新生血管膜(CNVM)形成。
在35天的时间里,24只大鼠每日经口灌胃给予20mg/kg鲁米昔布,悬浮于0.5%(w/v)羧甲基纤维素钠(CMC)中,而对照组仅给予0.5% CMC悬浮液。7天后,在视盘周围同心放置8个激光光凝点以诱导CNVM形成。35天后,进行眼底摄影和荧光素血管造影(FA),并对眼睛进行组织病理学分析。
对病变部位进行盲法FA分级显示,治疗组(1.4)和对照组(1.7)眼睛的平均组间评分在晚期染色强度和渗漏方面存在微小但具有统计学意义的差异(P<0.0001)。组织病理学分析表明,鲁米昔布治疗组动物的CNVM平均厚度±标准差为38±19微米(n=24只眼,175个光凝点),与对照组动物的CNVM平均厚度±标准差54±20微米(n=24只眼,171个光凝点)相比,减少了30%(P<0.001)。
在大鼠激光损伤模型中,全身给予选择性COX-2抑制剂鲁米昔布可使CNVM形成部分但显著减少,因此作为渗出性年龄相关性黄斑变性中CNVM形成的潜在抑制剂可能具有临床益处。