Effects of TGF-beta and TGF-beta neutralizing antibodies on fibroblast-induced collagen gel contraction: implications for proliferative vitreoretinopathy.

The main cause of failure after retinal reattachment surgery is proliferative vitreoretinopathy (PVR), in which contractile fibrocellular membranes form on the retinal surface and vitreous base. Recently, elevated levels of transforming growth factor-beta 2 (TGF-beta 2) were measured in the vitreous of patients with PVR, suggesting a possible association with the disease. Because neutralizing TGF-beta may prove useful in controlling this blinding disease process, the authors examined the effect of anti-TGF-beta 1 and TGF-beta 2 antibodies in TGF-beta-mediated fibroblast-induced collagen gel contraction. Rabbit dermal fibroblasts were combined with type I collagen in an in vitro model of collagen gel contraction. The authors evaluated the effect of TGF-beta 1, TGF-beta 2, and their antibodies on fibroblast-induced gel contraction. TGF-beta 1 and TGF-beta 2 equally enhanced gel contraction to an average of 6% to 7% of the control area by day 4. In contrast, gels without TGF-beta contracted only to an average of 38% of the control gels. Several anti-TGF-beta antibodies neutralized this TGF-beta-enhanced contraction, whereas control IgGs had no effect. A dose-dependent response was detected with TGF-beta 1, TGF-beta 2, and anti-TGF-beta. Because TGF-beta levels have been shown to correlate with the severity of PVR, the neutralizing action of anti-TGF-beta on TGF-beta-mediated contraction may offer further insights into the structure and function of PVR membranes and may provide clues to possible therapeutic solutions for controlling this disease process.