Expression of transforming growth factor β and matrix metalloproteinases in the aqueous humor of patients with congenital ectopia lentis.

Abstract

It is well known that transforming growth factor β (TGFβ), which is able to stimulate multiple intracellular signaling pathways, exerts an important role in Marfan syndrome, although the effects of TGFβ on congenital ectopia lentis (CEL) have yet to be fully elucidated. In the present study, the expression levels of TGFβ and matrix metalloproteinases (MMPs) were investigated in the aqueous humor of patients with ectopic lentis who differed in terms of the severity of the disease. A total of 17 CEL patients with 21 eyes (aged 12.76±9.37 years) and 12 congenital cataract (CC) patients with 17 eyes (aged 6.82±9.18 years) were randomized in the present study. The levels of active TGFβ and MMPs in the aqueous humor were analyzed with Luminex xMAP® technology by using commercially available Bio-Plex Pro™ Human MMP and TGFβ assays. The distance from the lens edge to the pupil edge and the white to white corneal diameter (i.e. the horizontal distance between the borders of the corneal limbus) were measured, and the ratio was calculated as the degree of lens dislocation. The association between TGFβ and MMP levels and the degree of lens dislocation was analyzed using Spearman's correlation test. Compared with the patients with CC, the level of TGFβ2 in the patients with CEL was increased significantly. Specifically, the level of TGFβ2 in the CEL patients was 855.19 pg/ml (744.33, 1,009.24), whereas it was 557.08 (438.24, 692.71) pg/ml in the CC patients (P<0.001). In addition, it was noted that the levels of MMP-2 and −10 in the aqueous humor of the patients with CEL were higher compared with those in the CC patients, although this increase did not reach the level of statistical significance. Notably, the levels of MMP-8 and −9 in the aqueous humor of patients with CEL were significantly lower compared with those in the CC patients (P=0.014 and P=0.002, respectively). Furthermore, a marginal correlation was identified between the severity of ectopic lentis and the levels of TGFβ2 in the aqueous humor (r2=0.379; P=0.003) of the patients with CEL. Taken together, these results demonstrated that a significant correlation existed between high levels of aqueous humor TGFβ2 and the severity of ectopia lentis in patients with CEL. In addition, aqueous humor TGFβ2 levels in the CEL patients were significantly higher compared with those in CC patients.