P 765Matrix metalloproteinases and metalloproteinase inhibitors in epiretinal membranes and choroidal neovascular membranes
U. E. K. Schnurrbusch, S. Wolf, S. Hoffmann, F. Gölfert1, R. H. W. Funk1, P. Wiedemann
Purpose: Matrix metalloproteinases (MMP) are a group of extracellular matrix degrading enzymes involved in physiological and pathological process associated with neovascularisation. To investigate the possible role of these enzymes and tissue inhibitors of metalloproteinases (TIMPs) we analysed epiretinal fibrovascular membranes from patients with proliferative diabetic retinopathy (PDR) and choroidal neovascular membrans (CNV) secondary to age related macular degeneration (AMD).
Methods: Surgically removed membranes from ten patients with PDR and ten patients with AMD were analyzed for the expression of MMP and TIMP mRNA. In situ hybridization antisense and sense riboprobes were generated using DNA complementary to human collagenase (MMP-1), 72 kDa gelatinase (MMP-2), stromelysin (MMP-3), 92 kDa gelatinase (MMP-9), TIMP-1, TIMP-2 and TIMP-3. Vascular endothelial cells in areas of neovaskularisation were stained with von Willebrand factor and caveolin.
Results: MMP-2 and MMP-9 mRNA were detected in all membranes (AMD and PDR). The decity of the MMPs was much higher in PDR membrans as in CNV. The membranes expressed TIMP-1, TIMP-3 mRNA. MMP-2, TiMP-1 and TIMP-2 mRNA had similar overall distribution within the vascularized stroma of the membranes. MMP-2 expression appeared to be localized mainly to the vascular endothelial cells, whereas TIMP-1 and TIMP-3 were detected in fibroblastic areas. MMP-9 was distinctly expressed by cells at the margins of the membrans and often in proximity to a thickened Bruch`s membrane layer. TIMP-3 mRNA was strongly expressed within the retinal pigment epithelial cell layer. None of the mebranes showed detectable MMP-1 or MMP-3 expression.
Conclusion: Metalloproteinases and their endogenous inhibitors are present in epiretinal fibrovascular membranes from patients with PDR and in CNV membranes from patients with AMD. The results support a role of MMPs in the development of choroidal neovascularization in AMD and in other vitreoretinal diseases, like PDR.
Klinik und Poliklinik für Augenheilkunde, Liebigstraße 10-14, D-04103 Leipzig, and 1Technische Universität Dresden, Institut für Anatomie, Fetscherstrasse 74, D-01307 Dresden