Levels and activation of matrix metalloproteinases in aqueous humor are elevated in uveitis-related secondary glaucoma.

PURPOSE

To measure the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2 and to study the expression pattern and molecular forms of MMP-2, 8, 9, 13, and 14 and TIMP-1 and 2 in aqueous humor samples in cases of uveitis-related secondary glaucoma (USG) with a history of up to 20 years by comparison with primary open-angle glaucoma (POAG) and cataracts.

METHODS

33 aqueous humor samples were collected during intraocular surgery. MMP-2 and TIMP-2 levels were analyzed by enzyme-linked immunosorbent assay. Molecular forms and activation degrees of MMPs and TIMPs were analyzed by Western immunoblotting and zymography. The results were related to the clinical data.

RESULTS

Enzyme-linked immunosorbent assay measurements of both MMP-2 and TIMP-2 were statistically significantly increased in the USG samples relative to POAG and cataracts (P=0.002). In Western blotting all the MMPs showed increased expression and conversion to their active forms in USG, whereas in the POAG and cataract samples MMPs were found mainly in their latent forms. MMP-8, 9, 13, and 14 showed statistically significantly elevated expression in USG relative to POAG and cataracts on densitometric scanning of Western blots. On zymography, MMP-2 and 9 activation was significantly enhanced in USG compared with POAG and cataracts.

CONCLUSIONS

Increased expression of MMPs and their conversion to active forms is characteristics of the aqueous humor in USG, even with a very long history. This emphasizes the fact that increased MMP expression reflects inflammatory disease activity and is probably associated with the development of USG and its complications. Although intraocular pressure is elevated in both glaucoma types, MMP expression in POAG more closely resembles that in cataracts, and therefore the role of MMPs in USG differs very markedly from that in POAG.