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From the Wound Healing Research and Glaucoma Units, Moorfields Eye Hospital and Institute of Ophthalmology, London, United Kingdom.
Abstract
PURPOSE. Currently available anti-scarring regimens for glaucoma filtration surgery have potentially blinding complications and thus the need for alternative and safer agents. The effects of a new antibody to transforming growth factor (TGF)-ß2 on in vitro and in vivo conjunctival scarring and after glaucoma filtration surgery were investigated.
METHODS. The activity of a novel recombinant monoclonal neutralizing antibody (mAb) to human TGF-2 (rhAnti-TGF-ß2 mAb) was studied in conjunctival fibroblast-mediated proliferation, migration, and collagen contraction. Its safety in subconjunctival administration was assessed in vivo, and, in a rabbit model of glaucoma filtration surgery, its effects on conjunctival scarring and filtration surgery outcome were investigated.
RESULTS. The rhAnti-TGF-ß2 mAb effectively inhibited TGF-ß2–mediated conjunctival scarring activity in vitro, at 50% inhibitory concentrations (IC50) of less than 1 nM. It significantly improved glaucoma filtration surgery outcome in an animal model of aggressive conjunctival scarring compared with control (P = 0.0291) and was clinically safe, nontoxic, and well tolerated after subconjunctival administration.
CONCLUSIONS. Subconjunctival rhAnti-TGF-ß2 mAb treatment significantly affects surgical outcome and effectively reduces conjunctival scarring both in vitro and in vivo. It appears safe for subconjunctival administration and when compared with mitomycin-C treatment histologically, much less destructive to local tissue. rhAnti-TGF-ß2 mAb may have potential as a new anti-scarring agent for use in glaucoma filtration surgery.
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