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Impressum
Matrix metalloproteinases expression by trabecular meshwork cells of different age under influence of dexamethasone or interleukin-1 and increased hydrostatic pressure
1Ehrich D., 2Tripathi R., 1Duncker G.
1Klinik und Poliklinik für Augenheilkunde, Martin-Luther Universität Halle- Wittenberg, Halle/Saale; 2Vision Research Laboratories, University of South Carolina, Columbia, SC, USA
Purpose: To evaluate the in vitro expression of MMP-1, -2, -3
and -14 as well as TIMP-1 and-2 in porcine trabecular meshwork cells of
different age under influence of increased hydrostatic pressure, and their
modulation by dexamethasone or interleukin-1b.
Methods: Primary (2 weeks) or tertiary (6 weeks) cell cultures
were exposed to 15 or 50 mm Hg. The cells were treated with serum-free
medium, 10ng/ml IL-1b or 10nM dexamethasone. Total RNA was extracted from
the harvested cells, reversed transcribed, amplified using specific primers,
and semi-quantified by laser densitometry.
Results: 6 weeks old trabecular cells expressed significant less
amounts of MMP and TIMP mRNA than the cells in the 2 weeks group. Increased
hydrostatic pressure up-regulated the expression of MMP-3 5-fold, MMP-2
1.8-fold and MMP-14 1.5-fold. Interleukin-1b increased the mRNA expression
for all evaluated MMPs and TIMPs in different extent. In comparison, dexamethasone
down-regulated the mRNA expression for all MMPs and TIMP-2, whereas TIMP-1
was unchanged.
Conclusions: Porcine trabecular meshwork cells responded in vitro
to increased hydrostatic pressure with a change in MMP and TIMP expression
which suggest that in case of increased intraoculare pressure some remodelling
of the extracellulare matrix may occur. Interleukin-1b and dexamethasone
as a model of pro- as well as anti-inflammatory influence modulated the
MMP and TIMP expression and subsequently the ECM turnover, too. The reduction
in mRNA expression under dexamethasone treatment is perhaps one reason
for the accumulation of some GAGs , followed by an increase of outflow
resistance in the trabecular meshwork in case of a steroid glaucoma.