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TGF-beta1, -beta2, and -beta3 in vitro: biphasic effects on Tenon's fibroblast contraction, proliferation, and
M F Cordeiro1, S S Bhattacharya, G S Schultz
1Department of Pathology, Moorfields Eye Hospital & Institute of Ophthalmology, London, United Kingdom. m.cordeiro@ucl.ac.uk
Purpose:
To compare the effects of the three human transforming growth factor-beta (TGF-beta) isoforms and different concentrations of TGF-beta on human Tenon's capsule fibroblasts (HTF), with a view to delineating the role of this growth factor in the subconjunctival scarring response after glaucoma filtration surgery.
Methods:
Application of recombinant human TGF-beta1, -beta2, and -beta3 (range 0-10(-8) M) was assessed using several assays of HTF function: fibroblast-mediated collagen contraction, proliferation, and migration.
Results:
All three isoforms of TGF-beta behaved in a similar manner in vitro. They each stimulated HTF-mediated collagen contraction, proliferation, and migration with a characteristic concentration-dependent response, with peak activities at 10(-9), 10(-12), and 10(-9) M, respectively, that were significantly different from control (P<0.05). At concentrations above and below peak activities, HTF activity was reduced, demonstrating biphasic effects of TGF-beta.
Conclusions:
TGF-beta1, -beta2, and -beta3 have similar actions in vitro; this is demonstrated by their effects on several HTF-mediated functions. TGF-beta induces a response in HTF that is concentration-dependent, with different functions being maximally stimulated at different concentrations. This biphasic response highlights the significance of the concentration profile of TGF-beta at the wound site. These findings are important in filtration surgery, where constant changes in the local environment occur due to the passage of aqueous and the wound healing process. The varying levels of TGF-beta in the aqueous and subconjunctival tissues may thus significantly modify the conjunctival scarring response.