豚鼠形觉剥夺早期后极部巩膜基质金属蛋白酶2及其抑制剂动态表达

Early expression of matrix metalloproteinase-2 and its tissue inhibitor in the posterior fibrous sclera of guinea pig eyes with form-deprivation myopia

目的探讨豚鼠形觉剥夺性近视(form-deprivation myopia,FDM)早期后极部巩膜基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)及基质金属蛋白酶抑制剂2(tissue inhibitor of matrix metalloproteinase-2,TIMP-2)mRNA的表达。方法4周龄三色豚鼠50只,随机分成实验组和正常对照组各25只,实验组又随机分为5组,单眼形觉剥夺(monocular deprivation,MD)右眼1、4、7、14、21 d制备FDM动物模型,未遮盖眼为自身对照组。各组豚鼠进行检影验光和A超测量眼轴长度。提取后极部巩膜总RNA,二步法逆转录聚合酶链反应检测各组后极部巩膜MMP-2及TIMP-2 mRNA的表达水平。结果除1 d外,各组MD后极部巩膜MMP-2 mRNA的表达与正常对照组、自身对照组差异均有统计学意义(P<0.05),MD组间差异也有统计学意义(P<0.01);而TIMP-2 mRNA的表达则逐渐下降。各自身对照组MMP-2、TIMP-2 mRNA的表达与MD组变化趋势大致相同。结论MMP-2/TIMP-2之间动态平衡失调可能是启动豚鼠FDM巩膜细胞外基质早期主动重塑的重要因素。

Objective To investigate the early expression of matrix metalloproteinase-2 （MMP-2） and its tissue inhibitor（TIMP-2） mRNA in posterior sclera of guinea pig eyes with form-deprivation myopia （FDM）. Methods Fifty 4-week-old guinea pigs were divided randomly and equivalently into experimental and control group, with 25 in each group. The experimental group was further divided randomly and equivalently into five groups, in which the right eye of each guinea pig was made monocular deprivation（MD） at 1,4,7,14 and 21 day respectively to induce FDM, the left eye served as self-control. After removing the goggle at every experimental point, the refractive status and the axial lengths were determined with streak retinoscopy （ without cycloplegia） and A-scan ultra-sonography under topical anaesthesia re- spectively. Both eyes were collected after guinea pigs were killed, and the total RNA in the posterior sclera was extracted traditionally using TRIZOL two-step reverse transcription-polymerase chain reaction. Results Compared with normal and self-controlled groups, the levels of MMP-2 mRNA expression in the posterior sclera of guinea pig with MD were higher, except for MD at 1 d. It was statistically different between MD and the control groups（P 〈0.05） and among the five MD groups（P 〈 0.01 ）. However,TIMP-2 mRNA expression was decreased. The change in the levels of MMP-2 and TIMP-2 mRNA expression in the posterior sclera of each self-controlled groups was similar to that of each MD groups. Conclusions Imbalance between expression of MMP-2 and TIMP-2 mRNA would probably be an important factor to trigger early scleral extracellular matrix （ECM） remodeling process to develop FDM by degradating scleral ECM excessively. （Chin J Ophthalmol and Otorhinolaryngo1,2010 ,10 ：75-78 ）