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Abstract #10706 Published in IGR 6-2
Effect of cyclical mechanical stretch and exogenous transforming growth factor-β1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head
Kirwan RP; Crean JK; Fenerty CH; Clark AF; O'brien CJJournal of Glaucoma 2004; 13: 327-34
PURPOSE: Extensive remodeling of the lamina cribrosa extracellular matrix occurs in primary open angle glaucoma. The transforming growth factor-beta (TGF-β) and matrix metalloproteinase (MMP) protein families are implicated in this process. The authors investigated (a). the effect of cyclical mechanical stretch on TGF-β1 mRNA synthesis, TGF-β1 protein secretion, MMP-2 protein activity and (b). the effect of exogenous TGF-β1 on MMP-2 protein activity in human lamina cribrosa cells in vitro. METHODS: Primary human lamina cribrosa cells grown on flexible and rigid plates were exposed to cyclical stretch (1Hz, 15%) or static conditions for 12 and 24 hours. Cells grown on 100-mm plates were exposed to human TGF-β1 (10 ng/ml) or vehicle (4 mM HCl/1% BSA) for 24 hours. TGF-β1 mRNA synthesis in stretched and static cells was measured using real-time polymerase chain reaction. TGF-β1 protein secretion in stretched and static cell media was measured using enzyme linked immunosorbent assay. Gelatin zymography measured MMP-2 activity in stretched, static, TGF-β1- treated and vehicle-treated cell media. RESULTS: Cyclical stretch induced significant increases in TGF-β1 mRNA synthesis after 12 hours (**P < 0.01) and TGF-β1 protein secretion after 24 hours (*P < 0.05). Cyclical stretch significantly (*P < 0.05) increased MMP-2 activity in cell media after 24 hours. Exogenous TGF-beta 1 induced a significant (**P < 0.01) increase in cell media MMP-2 activity after 24 hours. CONCLUSIONS: These results suggest that cyclical stretch and TGF-β1 modulate MMP-2 activity in human lamina cribrosa cells. TGF-beta 1 and MMP-2 release from lamina cribrosa cells may facilitate matrix remodeling of the optic nerve head in primary open angle glaucoma.
Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. ruaidhri.kirwan@ucd.ie
Classification:
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
