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. 2000 Oct;84(10):1091–1096. doi: 10.1136/bjo.84.10.1091

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

J Salzmann 1, G Limb 1, P Khaw 1, Z Gregor 1, L Webster 1, A Chignell 1, D Charteris 1
PMCID: PMC1723275  PMID: 11004090

Abstract

AIM—To examine epiretinal membranes of proliferative diabetic retinopathy (PDR) for the presence of selective matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), in order to determine whether neovascularisation 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 fibrovascular epiretinal membranes of PDR, and the findings compared with that observed in 21 avascular epiretinal membranes of proliferative vitreoretinopathy (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 metalloproteinases (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%) stained 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 perivascular matrix of PDR membranes, and there was a significant increase in TIMP-2 expression by PDR membranes (p= 0.036) when compared with PVR membranes.
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 proportion of PDR membranes, and that their expression does not differ from that of PVR membranes, suggest the existence of common pathways of extracellular matrix degradation in pathological processes leading to retinal neovascularisation and fibrosis.



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Figure 1  .

Figure 1  

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Photomicrographs of PDR membranes showing deposition of selective MMPs and TIMPs. The pink precipitate indicates the presence of these molecules within the membranes. Specimens were counterstained with Mayer's haematoxylin. (A) PDR membrane (No 15) showing strong staining (+++) for MMP-1. (B) PDR membrane (No 12) showing intense cellular and extracellular staining (+++) for MMP-2. (C) PDR membrane (No 1) exhibiting staining for MMP-9 within the extracellular and perivascular matrix. (D) Section of PDR membrane (No 17) showing detail staining for MMP-9 in the perivascular matrix. (E) PDR membrane exhibiting moderate staining (++) for TIMP-1 (No 11). (F) Normal retina showing negative staining for MMP-9.

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