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Editors Selection IGR 17-4
Basic research: TGF-beta
Comment by Jonathan Crowston on:
13274 Induction of TGF-β1 in the trabecular meshwork under cyclic mechanical stress, Liton PB; Liu X; Challa P et al., Journal of Cellular Physiology, 2005; 205: 364-371
The pathophysiology that leads to obstructed aqueous humor outflow in the trabecular meshwork in glaucoma is not fully understood. Mechanical stress is emerging as an important regulator of homeostasis in many tissues including the trabecular meshwork (TM), which is distended and stretched during IOP elevation. Liton et al. (31) investigated the effect of cyclic mechanical stress on transforming growth factor (TGF-β1) expression in cultured human trabecular meshwork cells as well as in perfusion studies of cultured of human anterior segments.
Using elegant techniques, they demonstrated that cyclic mechanical stress increased both total and biologically active TGF-β 1 protein in primary cultures of human trabecular meshwork cells, which was associated with activation of the TGF-beta promoter. IOP fluctuation between 12 and 18 mmHg in a perfusion model of human anterior segment organ culture, also led to the accumulation of TGF-β 1 in the TM extracellular matrix and TGF-β 1 promoter activation was localized to cells of the outflow pathways.
The authors propose that while mechanical stretch-induced expression of TGF-β 1 may have an important role in the homeostatic regulation of extracellular matrix synthesis in the trabecular meshwork, aberrant expression of TGF-β 1 in response to chronic mechanical stress may also contribute to the pathological changes in these tissues in certain types of glaucoma. Although it is not clear how the cyclical mechanical stress applied in these models relates to the mechanical stress that is encountered by the TM in vivo. These models do provide experimental means for determining the molecular pathways that regulate extracellular matrix in the trabecular meshwork and thus may identify new therapeutic targets for lowering IOP.
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