Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy

Aim-To examine epiretinal membranes of proliferative diabetic retinopathy ( PDR) for the presence of selective matrix metalloproteinases (MMPs) and the ir natural inhibitors (TIMPs), in order to determine whether neovascularisa tion and fibrosis, characteristic of this complication of diabetes mellitus , are associated with specific anomalies of MMP or TIMP expression. Methods-The presence of selected MMPs and TIMPs was investigated in 24 fibr ovascular epiretinal membranes of PDR, and the findings compared with that observed in 21 avascular epiretinal membranes of proliferative vitreoretino pathy (PVR) and five normal retinas. Specimens were examined for deposition of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase A ( MMP-2), gelatinase B (MMP-9), and three tissue inhibitors of metalloprotein ases (TIMP-1, TIMP-2, and TIMP-3). Results-The results showed that unlike normal retina, which constitutively expresses MMP-1 and TIMP-2, a large proportion of PDR membranes (> 62%) sta ined for MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and TIMP-3. There were no differences in the expression of these molecules when compared with PVR membranes. A characteristic staining for MMP-9 was observed within the per ivascular matrix of PDR membranes, and there was a significant increase in TIMP-2 expression by PDR membranes (p = 0.036) when compared with PVR membr anes. Conclusions-The findings that MMPs involved in degradation of fibrovascular tissue matrix, as well as TIMP-1 and TIMP-2, are found in a large proporti on of PDR membranes, and that their expression does not differ from that of PVR membranes, suggest the existence of common pathways of extracellular m atrix degradation in pathological processes leading to retinal neovasculari sation and fibrosis.