Background The domestic and international researches discovered that many proteins and enzymes of the extracellular matrix (ECM) participate in the sclera remodeling by affecting the collagen typeⅠand fibronectin.Objective This study was to investigate the effect of matrixmetalloproteinase-2 (TIMP-2) on expression of collagen typeⅠand fibronectin of ECM in the posterior sclera by injecting liposomes containing tissue inhibitor of TIMP-2 gene into suprachoroidal space of the form-deprivation myopia in guinea pig.Methods Form-deprivation myopia was induced by translucent goggles in 36 clean guinea pig for 2 weeks.Then the animals were randomly assigned to TIMP-2 group,empty plasmid group,saline group and 12 for each group.Liposomes of 5μl containing TIMP-2 gene,empty plasmid and saline were suprachoroidally injected in the right eye respectively,and the left eyes without any treatment were used as self-control group.Other 12 matched guinea pigs only covered the right eyes through out the experimental duration as model control group.The guinea pigs were sacrificed and the posterior sclera tissue of the eyeballs were collected at 2,7 and 14 days after injection of drug.The expressions of collagen typeⅠmRNA and fibronectin mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).This study followed the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The expression level of collagen type Ⅰ mRNA in the posterior sclera of guinea pig was lower but that of fibronectin mRNA was higher in TIMP-2 group than self-control group,showing significant differences between them (P＜0.05).The expression level of collagen type Ⅰ mRNA in the posterior scleral tissue began to increase from the 2nd day after drug injection and was obviously elevated at the 7th day and then gradually decreased at the 14th day.However,the expression level of fibronectin mRNA in the posterior scleral tissue showed the opposite pattern.The expression levels of collagen typeⅠmRNA and fibronectin mRNA at the 7th after drug injection were significantly lower than that at the 2nd day or 14th day (P＜0.01).Conclusion Suprachoroidal injection of TIMP-2 in form-deprivation myopia could up-regulate the expression of collagen typeⅠmRNA and down-regulate the expression of fibronectin mRNA in the posterior scleral tissue.It may slow down the sclera remodeling of form-deprivation myopia in guinea pig in the early stage.%背景 细胞外基质(ECM)蛋白和酶参与眼球后极部巩膜主动的重塑过程,主要通过影响Ⅰ型胶原蛋白(Col-Ⅰ)纤维连接蛋白(FN)发挥作用.目的 通过对形觉剥夺性近视(FDM)豚鼠经脉络膜上腔注入转染有TIMP-2基因的脂质体,观察基质金属蛋白酶抑制剂-2(TIMP-2)对细胞外基质中Ⅰ型胶原蛋白(Col-Ⅰ)和FN mRNA 表达的影响.方法 半透明眼罩遮盖36只豚鼠的右眼14d建立FDM动物模型,用随机数字表法分组后分别于右眼脉络膜上腔注入5μl TIMP-2脂质体质粒、空质粒和生理盐水,每组12只眼,左眼为自身对照.另12只豚鼠持续遮盖右眼为模型对照组.分别于脉络膜上腔注药后的2、7、14d过量麻醉处死豚鼠,获取眼球后极部巩膜组织,用RT-PCR法分别检测各组豚鼠眼巩膜组织中Col-Ⅰ和FN mRNA 的表达.结果 TIMP-2组豚鼠后极部巩膜Col-Ⅰ mRNA表达降低,FN mRNA表达升高,与自身对照相比差异均有统计学意义(P＜0.05).注入TIMP-2后,Col-Ⅰ mRNA表达水平从第2天开始升高,第7天达到高峰,第14天时有所回落;FN mRNA表达水平则呈相反变化.二者在第7天、第14天的表达与其他3组间比较差异均有统计学意义(P＜0.05).Col-ⅠmRNA和FN mRNA表达水平在注射后第7天与第2天或第14天比较差异均有统计学意义(P＜0.01).结论 TIMP-2注入FDM豚鼠脉络膜上腔可上调Col-Ⅰ mRNA表达,下调FN mRNA表达,早期可有减缓豚鼠FDM巩膜重塑的作用.
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