The Effect of Integrin Antibodies on the Attachment and Proliferation of Human Tenon's Capsule Fibroblasts

Abstract

The integrins are protein heterodimers consisting of noncovalently associated α and β subunits. The adhesive interactions mediated by integrins are necessary for cellular survival and proliferation. In this study we investigated the effects of three different integrin antibodies on the proliferation of human Tenon's capsule fibroblasts in tissue culture. Human Tenon's capsule fibroblasts were cultured into 96 well plates and treated with different concentrations (ranging from 10−6to 1 μg ml−1) of three different integrin antibodies: human integrin α-2 antibody, human integrin α-3 antibody and human integrin α-5/FnR (fibronectin receptor) antibody. Coulter counter, hexosaminidase, and3H-thymidine assays were used to determine the inhibitory effects of these integrin antibodies on ocular fibroblasts on days 0 (attachment), 1,3 and 7 following antibody treatment. The concentration of each antibody required to produce a proliferation 50% less than the control (ID50) was calculated for each assay. With respect to attachment, all three antibodies studied displayed some inhibitory activity. All three antibodies also displayed dose-dependent antiproliferative properties, especially at the highest concentration tested after 7 days of exposure. The integrin α-2 antibody was the most potent of the inhibitors, followed by the integrin α-3 antibody, with the integrin α-5 antibody being the least potent antibody tested. In addition, the anti-proliferative activities of the integrin α-2 and integrin α-3 antibodies increased with increasing incubation time. In conclusion, these integrin antibodies demonstrated some inhibitory effects on the attachment and proliferation of human Tenon's capsule fibroblasts in culture. Further investigation will be required to determine whether integrin antibodies can significantly limit scar formation in vivo without significant toxicity.