advertisement
Abstract #9674 Published in IGR 5-3
The effect of TGF-β2 on human trabecular meshwork extracellular proteolytic system
Fuchshofer R; Welge-Lussen U; Lütjen-Drecoll EExperimental Eye Research 2003; 77: 757-765
This study aimed to investigate whether transforming growth factor-β2 (TGF-β2), increased in the aqueous humor of eyes with primary open angle glaucoma (POAG), can affect factors responsible for the activity of matrix metalloproteinases (MMPs) in human trabecular cell cultures. With this goal in mind cultures of human trabecular meshwork (hTM) cells derived from eight donors were treated with TGF-β2 for 24, 36 and 48 hours. Influence of TGF-β2 on the expression of MMP-2, MMP-9, membrane type 1-MMP (MT1-MMP) and plasminogen activator inhibitor-1 (PAI-1) was examined using RT-PCR, northern blot, western blot, and zymography. The influence of TGF-β2 treatment on PAI-1 expression was also investigated using immunohistochemistry. It appeared that treatment with TGF-β2 significantly increased expression of the proform of MMP-2, whereas the active form was not detectable. MMP-9 and MT1-MMP expression were not influenced by TGF-β2 treatment. There was, however, a significant increase in PAI-1 expression. In order to investigate whether transformation of the proform of MMP-2 to the active form was inhibited by PAI-1, the influence of treatment with TGF-β2 and a PAI-1 neutralizing antibody on MMP-2 was investigated using the zymogram method. With this treatment protocol, the active form of MMP-2 was clearly visible, indicating that TGF-β2 enhancement of the PAI-1-expression decreases MMP activity. Inhibition of MMP activity through elevated levels of TGF-β2 might contribute to the increase in ECM in the trabecular meshwork of glaucomatous eyes.
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)