Yoo Ae Ri, Chung Sung Kun
*Department of Ophthalmology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea; and †Department of Ophthalmology and Visual Science, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 137-701, Republic of Korea.
Cornea. 2014 Oct;33(10):1088-94. doi: 10.1097/ICO.0000000000000220.
The aim of this study was to compare the antiangiogenic effects of subconjunctival application of bevacizumab and tocilizumab on the regression of corneal neovascularization (NV) in rabbits.
Corneal neovascularization was induced in 48 eyes of 24 rabbits. Seven days after suture placement, the rabbits were divided into 4 groups of 6 rabbits each and treated subconjunctivally with 0.1 mL balanced salt solution (group 1), 0.1 mL tocilizumab (0.25 mg per 0.1 mL and 2.5 mg per 0.1 mL, groups 2 and 3), or 0.1 mL bevacizumab (2.5 mg per 0.1 mL) (group 4). Digital photographs of the eyes were obtained and the surface areas of corneal neovascularization were measured on days 7 and 14 after subconjunctival injections. On days 7 and 14, 3 rabbits were randomly chosen and the eyes were extracted. Half of the corneal specimens were analyzed histopathologically, and the other half were used to measure the concentrations of vascular endothelial growth factor (VEGF) and IL-6 using a multiplex bead assay, and the levels were compared with those of the controls.
The surface areas of induced corneal neovascularization were significantly smaller in groups 3 and 4 (2.5 mg of tocilizumab and 2.5 mg of bevacizumab) compared with the control group on days 7 and 14 (P < 0.05). Group 2 did not show significant difference from the control group on days 7 and 14. There were no differences observed in the reduced neovascularization areas in groups 3 and 4 on days 7 and 14. The concentrations of VEGF in groups 3 and 4 were significantly lower than in the control group, and IL-6 mRNA levels were significantly lower in group 3 than in the other groups (P < 0.001) on days 7 and 14. Immunohistochemical analysis confirmed the reduced expression of VEGF in all 3 experimental groups compared with the control group.
An antiangiogenic effect was observed after subconjunctival injection of 2.5 mg tocilizumab to an extent similar to that seen with 2.5 mg bevacizumab, which indicates that subconjunctival application of tocilizumab is effective for the inhibition of corneal neovascularization.
本研究旨在比较结膜下注射贝伐单抗和托珠单抗对兔角膜新生血管（NV）消退的抗血管生成作用。
对24只兔的48只眼诱导角膜新生血管形成。缝线放置7天后，将兔分为4组，每组6只，分别结膜下注射0.1 mL平衡盐溶液（第1组）、0.1 mL托珠单抗（每0.1 mL含0.25 mg和2.5 mg，第2组和第3组）或0.1 mL贝伐单抗（每0.1 mL含2.5 mg）（第4组）。在结膜下注射后第7天和第14天获取眼部数码照片并测量角膜新生血管的表面积。在第7天和第14天，随机选择3只兔并摘除眼球。一半角膜标本进行组织病理学分析，另一半用于通过多重微珠分析测量血管内皮生长因子（VEGF）和IL-6的浓度，并将水平与对照组进行比较。
在第7天和第14天，第3组和第4组（2.5 mg托珠单抗和2.5 mg贝伐单抗）诱导的角膜新生血管表面积与对照组相比显著更小（P < 0.05）。第2组在第7天和第14天与对照组无显著差异。第7天和第14天，第3组和第4组在新生血管减少面积方面未观察到差异。在第7天和第14天，第3组和第4组的VEGF浓度显著低于对照组，第3组的IL-6 mRNA水平显著低于其他组（P < 0.001）。免疫组织化学分析证实，与对照组相比，所有3个实验组中VEGF的表达均降低。
结膜下注射2.5 mg托珠单抗后观察到抗血管生成作用，其程度与2.5 mg贝伐单抗相似，这表明结膜下应用托珠单抗对抑制角膜新生血管有效。
