Human anti-transforming growth factor-beta 2 antibody: A new glaucoma anti-scarring agent

PURPOSE. Currently available anti-scarring regimens for glaucoma filtration surgery have potentially blinding complications and thus the need for alte rnative and safer agents. The effects of a new antibody to transforming gro wth factor (TGF)-beta 2 on in vitro and in vivo conjunctival scarring and a fter glaucoma filtration surgery were investigated. METHODS. The activity of a novel recombinant monoclonal neutralizing antibo dy (mAb) to human TGF-2 (rhAnti-TGF-beta 2 mAb) was studied in conjunctival fibroblast-mediated proliferation, migration, and collagen contraction. It s safety in subconjunctival administration was assessed in vivo, and, in a rabbit model of glaucoma filtration surgery, its effects on conjunctival sc arring and filtration surgery outcome were investigated. RESULTS. The rhlAnti-TGF-beta 2 mAb effectively inhibited TGF-beta 2-mediat ed conjunctival scarring activity in vitro, at 50% inhibitory concentration s (IC50) of less than 1 nM. It significantly improved glaucoma filtration s urgery outcome in an animal model of aggressive conjunctival scarring compa red with control (P = 0.0291) and was clinically safe, nontoxic, and well t olerated after subconjunctival administration. CONCLUSIONS. Subconjunctival rhAnti-TGF-beta 2 mAb treatment significantly affects surgical outcome and effectively reduces conjunctival scarring both in vitro and in vivo. It appears safe for subconjunctival administration a nd when compared with mitomycin-C treatment histologically, much less destr uctive to local tissue, rhAnti-TGF-beta 2 mAb may have potential as a new a nti-scarring agent for use in glaucoma filtration surgery.