Reviglio Victor E, Hakim Melinda A, Song Jae K, O'Brien Terrence P
Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.
BMC Ophthalmol. 2003 Oct 6;3:10. doi: 10.1186/1471-2415-3-10.
Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea.
Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Uniform corneal epithelial defects were created in the right eye with application of 75% alcohol in the center of the tissue for 6 seconds. The treatment groups were tested as follows: 1) Tear drops: carboxymethylcellulose sodium 0.5 % (Refresh, Allergan); 2) Ciprofloxacin 0.3% (Ciloxan, Alcon); 3) Ofloxacin 0.3%(Ocuflox, Allergan); 4) Levofloxacin 0.5%(Quixin, Santen). Eye drops were administered 6 times a day for 48 hours. Rats were sacrificed at 48 hours. Immunohistochemical analysis and zymography were conducted using antibodies specific to MMPs-1, 2, 8 and 9.
MMP-1, MMP-2, MMP-8 and MMP-9 expression were detected at 48 hrs in undebrided corneal epithelium groups treated with the topical fluoroquinolones. No statistical difference was observed in quantitative expression of MMPs among ciprofloxacin 0.3%, ofloxacin 0.3%, levofloxacin 0.5%. When the artificial tear group and the fluoroquinolone groups with corneal epithelial defect were compared, increased expression of MMPs was observed as a result of the wound healing process. However, the fluoroquinolone treated group exhibited high statistically significantly levels of MMPs expression.
Our study provides preliminary evidence that topical application of fluoroquinolone drugs can induce the expression of MMP-1, MMP-2, MMP-8 and MMP-9 in the undebrided corneal epithelium compared to artificial tear eye drops.
基质金属蛋白酶在细胞外基质的沉积和降解中起重要作用。基于先前局部使用氟喹诺酮治疗期间角膜穿孔的临床观察，我们决定评估各种氟喹诺酮眼药水对角膜中基质金属蛋白酶（MMPs）表达的比较影响。
80只雌性Lewis大鼠分为两个实验组：完整角膜上皮组和受伤角膜上皮组。通过在组织中心应用75%酒精6秒在右眼造成均匀的角膜上皮缺损。治疗组如下测试：1）眼药水：0.5%羧甲基纤维素钠（Refresh，爱尔康）；2）0.3%环丙沙星（Ciloxan，爱尔康）；3）0.3%氧氟沙星（Ocuflox，爱尔康）；4）0.5%左氧氟沙星（Quixin，参天）。眼药水每天给药6次，共48小时。48小时后处死大鼠。使用针对MMPs-1、2、8和9的特异性抗体进行免疫组织化学分析和酶谱分析。
在用局部氟喹诺酮治疗的未清创角膜上皮组中，48小时时检测到MMP-1、MMP-2、MMP-8和MMP-9的表达。0.3%环丙沙星、0.3%氧氟沙星、0.5%左氧氟沙星之间MMPs的定量表达未观察到统计学差异。当比较人工泪液组和有角膜上皮缺损的氟喹诺酮组时，由于伤口愈合过程观察到MMPs表达增加。然而，氟喹诺酮治疗组显示出MMPs表达的统计学显著高水平。
我们的研究提供了初步证据，表明与人工泪液眼药水相比，局部应用氟喹诺酮药物可诱导未清创角膜上皮中MMP-1、MMP-2、MMP-8和MMP-9的表达。
