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Abstract #27053 Published in IGR 12-4
Antifibrotic Activity of Bevacizumab on Human Tenon's Fibroblasts In Vitro.
O'Neill EC; Qin Q; Van Bergen NJ; Connell PP; Vasudevan S; Coote MA; Trounce IA; Wong TT; Crowston JGInvestigative Ophthalmology and Visual Science 2010; 51: 6524-6532
See also comment(s) by Malik Kahook •
Purpose. To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenon's capsule fibroblasts (HTFs) in an in vitro model of wound healing. Methods. Fibroblasts were cultured in RPMI media, and bevacizumab was administered at a concentration ranging from 0.25 to 12.5 mg/mL. Fibroblast viability and cell death were assessed using the MTT colorimetric assay, lactate dehydrogenase assay, BrdU assay, and live/dead assay. Fibroblast contractility was assessed in floating collagen gels. Morphologic changes were assessed by transmission electron microscopy. Antifibrosis activities were compared with 5-fluorouracil. Results. Bevacizumab induced a significant dose-related reduction of HTF cell number at 12.5 mg/mL at 72 hours (P < 0.05). Under serum-free conditions, bevacizumab induced significant fibroblast cell death at concentrations greater than 7.5 mg/mL (P < 0.05). Bevacizumab caused a moderate inhibition of fibroblast gel contraction from baseline (P < 0.05). Scanning electron microscopy revealed marked vacuolization in bevacizumab-treated fibroblasts. Conclusions. Bevacizumab disrupted fibroblast proliferation, inhibited collagen gel contraction ability, and induced fibroblast cell death at concentrations greater than 7.5 mg/mL in serum-free conditions. These results demonstrated that bevacizumab inhibited a number of fibrosis activities in culture. These activities may underpin the antifibrosis effect proposed in vivo.
Centre for Eye Research Australia, the Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia;
Classification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
11.15 Other drugs in relation to glaucoma (Part of: 11 Medical treatment)
