TGF-beta 1, -beta 2, and -beta 3 in vitro: Biphasic effects on Tenon's fibroblast contraction, proliferation, and migration

Purpose, To compare the effects of the three human transforming growth fact or-beta (TGF-beta) isoforms and different concentrations of TGF-beta on hum an Tenon's capsule fibroblasts (HTF), with a view to delineating the role o f this growth factor in the subconjunctival scarring response after glaucom a filtration surgery. Methods. Application of recombinant human TGF-beta 1, -beta 2,and -beta 3 ( range 0-10(-8) M) was assessed using several assays of HTF function: fibrob last-mediated collagen contraction, proliferation, and migration. Results. All three isoforms of TGF-beta behaved in a similar manner in vitr o. They each stimulated HTF-mediated collagen contraction, proliferation, a nd migration with a characteristic concentration-dependent response, with p eak activities at 10(-9), 10(-12), and 10(-9) M, respectively, that were si gnificantly different from control (P < 0.05). At concentrations above acid below peak activities, HTF activity was reduced, demonstrating biphasic ef fects of TGF-beta. Conclusions. TGF-beta 1, -beta 2, and -beta 3 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 di fferent functions being maximally stimulated at different concentrations. T his biphasic response highlights the significance of the concentration prof ile of TGF-beta at the wound site. These findings are important in filtrati on surgery, where constant changes in the local environment occur due to th e passage of aqueous and the wound healing process. The varying levels of T GF-beta in die aqueous and subconjunctival tissues may thus significantly m odify the conjunctival scarring response.