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Abstract #15440 Published in IGR 1-3
Human anti-transforming growth factor-beta2 antibody: a new glaucoma anti-scarring agent
Cordeiro MF; Gay JA; Khaw PTInvestigative Ophthalmology and Visual Science 1999; 40: 2225-2234
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)-β2 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-β2 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-β2 mAb effectively inhibited TGF-β2-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-β2 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-β2 mAb may have potential as a new anti-scarring agent for use in glaucoma filtration surgery.
Dr. M.F. Cordeiro, Wound Healing Research Unit, Moorfields Eye Hospital and Institute of Ophthalmology, London; UK
