Matrix metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-9, and TIMP-1, TIMP-2 and TIMP-3) and markers for vascularization in functioning and non-functioning bleb capsules of glaucoma drainage implants

Abstract

Purpose To investigate and compare functioning versus non-functioning glaucoma drainage implant (GDI) capsules for selective markers of extracellular matrix degradation and vascularity. Methods In three samples of both functioning and non-functioning blebs, immunohistochemistry was used to determine the expression of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, TIMP-3 and CD31. A non-functioning bleb was defined as IOP >21 mmHg or <20% reduction in IOP from baseline with maximal tolerated medication. The samples were classified into five grades based on immunostaining: no staining, no significant staining, mild, moderate or marked staining. Results Expression of MMP-1, MMP-2 and MMP-3 was mostly low in both functioning and non-functioning blebs. However, immunostaining of MMP-9 was marked in samples taken from functioning GDIs and correlated with the presence of vascular profiles in the luminal bleb. CD31 immunoreactivity was more intense in the outer layers of the bleb than in the inner layers. In non-functioning blebs, immunoreactivity for TIMP-3 was significant through the whole bleb wall, but only mild in the inner zone of functioning blebs. TIMP-1 and TIMP-2 were barely detectable. Conclusion Staining of TIMP-3 was seen to be lower in the vicinity of the small blood vessels. In avascular bleb wall, increased expression of TIMP-3 suggests its potential role in the inhibition of angiogenesis as reported previously in vivo. The abundance of MMP-9 in bleb capsule wall of relatively old patients might lead to weakened bleb capsule wall architecture and increasing filtration of aqueous humour through the capsule, which are reflected in a lower IOP.