Retinal neovascularization is suppressed with a matrix metalloproteinase inhibitor.
Retinal neovascularization is suppressed with a matrix metalloproteinase inhibitor.
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DOI：
10.1001/archopht.117.4.498
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发表时间：
1999-04
影响因子：
--
通讯作者：
A. Das;A. McLamore;Wanmin Song;P. McGuire
中科院分区：
文献类型：
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作者：
A. Das;A. McLamore;Wanmin Song;P. McGuire
目的探讨细胞外蛋白酶在缺血视网膜新生动物模型中的作用，并探讨蛋白酶抑制剂对视网膜新生的影响。方法将新生小鼠暴露于75%氧气环境5 d，然后再暴露于室内空气中，诱导其视网膜新生血管形成。视网膜提取物进行酶谱分析以测定尿激酶和基质金属蛋白酶（MMPs）的活性。在相同条件下，一些动物还接受了腹腔注射MMP抑制剂。通过组织学分析来量化这些动物的新生血管反应。结果视网膜新生动物视网膜中尿激酶和MMPs （MMP-2和MMP-9）水平显著升高。腹腔注射MMP抑制剂可显著抑制新生血管。结论全身抑制MMPs可能具有预防视网膜新生血管相关视网膜病变的治疗潜力。由于蛋白酶的上调和激活是视网膜新生过程中最后的共同途径，因此对该途径的药物干预可能是增殖性视网膜病变的另一种治疗方法。
OBJECTIVES To determine the role of extracellular proteinases in ischemia-induced retinal neovascularization in an animal model and to examine the effect of proteinase inhibitors on retinal neovascularization. METHODS Retinal neovascularization was induced in newborn mice exposed to 75% oxygen for 5 days, followed by room air. Retinal extracts underwent zymographic analysis to measure the activity of urokinase and matrix metalloproteinases (MMPs). Some animals under the same conditions also received intraperitoneal injections of an MMP inhibitor. Histological analysis was done to quantitate the neovascular response in these animals. RESULTS Levels of urokinase and MMPs (MMP-2 and MMP-9) in retinas were significantly increased in animals with induced retinal neovascularization. Neovascularization was significantly inhibited with intraperitoneal administration of an MMP inhibitor. CONCLUSION Systemic inhibition of MMPs may have therapeutic potential in preventing retinopathy associated with retinal neovascularization. CLINICAL RELEVANCE Because up-regulation and activation of proteinases represents a final common pathway in the process of retinal neovascularization, pharmacological intervention of this pathway may be an alternative therapeutic approach to proliferative retinopathy.