Br J Ophthalmol 2000;84:1091-1096
( October )
Matrix metalloproteinases and their natural inhibitors in
fibrovascular membranes of proliferative diabetic retinopathy
Joel Salzmanna, G Astrid Limba, Peng T Khawa, Zdenek J Gregora, Lynne Websterb, Anthony H Chignellb, David G Charterisa
a Institute
of Ophthalmology and Moorfields Eye Hospital, London, UK, b St Thomas's Hospital, London
Correspondence to: Dr G A Limb, Department of Pathology, Institute of Ophthalmology,
11-43 Bath Street, London EC1V 9EL, UK
g.limb{at}ucl.ac.uk
Accepted for publication 23 May 2000
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.
© 2000 by British Journal of Ophthalmology
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