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Abstract #18512 Published in IGR 3-3
Increased hydrostatic pressure influences expression of matrix metalloproteases mRNAs by trabecular cells
Ehrich D; Tripathi B; Tripathi R; Duncker GResearch Communications in Pharmacology and Toxicology 2001; 6: 107-116
Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) have an important role in the enzymatic degradation and regulated turnover of extracellular matrix (ECM) molecules. Because the trabecular meshwork is exposed to raised intraocular pressure (IOP) in glaucomatous conditions of the eye, the authors investigated the effect of increased hydrostatic pressure on the expression of the mRNAs for MMPs and TIMPs by trabecular cells. Confluent primary cultures of porcine trabecular cells were exposed to pressures of 50 or 15 mmHg (corresponding to high and normal IOP, respectively) in specially designed chambers. After 72 hours, total RNA was extracted from the harvested cells, reversed-transcribed, and amplified using primers specific for MMP-1, -2, -3, and -14, for TIMP-1 and -2, and for GAPDH as internal control. PCR-amplified products with the expected sizes of 645, 500, 245, 555, 187, and 338 bp corresponding to the mRNAs for MMP-1, -2, -3, and -14, and TIMP-1 and -2, respectively, were obtained from trabecular cells exposed to 15 mmHg. In comparison, trabecular cells exposed to 50 mmHg showed a five-fold increase in mRNA for MMP-3, 1.75-fold for MMP-2, 1.5-fold for MMP-14, and 1.3- fold for both TIMP-1 and -2. No significant change was detected in the expression of the mRNA for MMP-1 and GAPDH. These results show that trabecular cells exposed to increased hydrostatic pressure exhibit a significant up-regulation of MMPs, except for MMP-1, and TIMPs. The authors suggest that remarkable remodelling of the ECM occurs in the trabecular meshwork in eyes with raised IOP. The balance between the accumulation of ECM and its turnover through the action of MMPs and TIMPs may provide one mechanism whereby outflow of aqueous humor regulated and IOP is controlled.
Dr R. Tripathi, Department of Ophthalmology, University of South Carolina, Columbia, SC, USA. rtripath@med.sc.edu
Classification:
2.5 Meshwork (Part of: 2 Anatomical structures in glaucoma)
