Different levels of TIMPs and MMPs in human lateral and medial rectus muscle tissue excised from strabismic patients

Abstract

PURPOSE To arrive at an understanding of the differences in gene and protein expression between human lateral and medial rectus muscle tissue excised from strabismic patients. METHODS Resected fragments of the lateral and medial rectus muscles obtained during strabismus surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill system. Radiolabelled cDNA was synthesized from polyA + RNA and hybridized with a gene array nylon membrane (Atlas Human 1.2 Array) to detect the difference in gene expression between the lateral and medial rectus muscles. Based on the gene array results, tissue inhibitor of metalloproteinases (TIMP)-1 and 2, matrix metalloproteinase (MMP)-2, and bone morphogenetic protein (BMP)-4 were measured in solubilized muscle tissues by enzyme immunoassay and normalized by unit length of resection. RESULTS The resected lateral rectus muscle had significantly smaller amounts of TIMP-1,TIMP-2 and BMP-4 but larger amounts of MMP-2 compared to the medial rectus muscle (P < 0.001, Mann-Whitney U test). The amounts of TIMP-1 in the muscle when the lateral and medial rectus were combined were positively correlated with TIMP-2 and BMP-4, while the amounts of TIMP-2 positively correlated with BMP-4 (P < 0.001, Spearman rank correlation test). The amounts of BMP-4 in both muscles increased significantly with age (P = 0.0003). CONCLUSIONS Resected tissue from the lateral and medial rectus muscles had different levels of expression of TIMP-1 and 2, MMP-2, and BMP-4. These molecular differences may underlie different characteristics of the two extraocular muscles and may also influence the process of wound healing after strabismus surgery.