Human anti-transforming growth factor-beta2 antibody: a new glaucoma anti-scarring agent.
OBJECTIVE
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)-beta2 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-beta2 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-beta2 mAb effectively inhibited TGF-beta2-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-beta2 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-beta2 mAb may have potential as a new anti-scarring agent for use in glaucoma filtration surgery.
Cordeiro
M F
MF
Wound Healing Research Unit, Moorfields Eye Hospital and Institute of Ophthalmology, London, United Kingdom.
Gay
J A
JA
Khaw
P T
PT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D002921:Cicatrix / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D003229:Conjunctival Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D018463:Filtering Surgery / Q000009:adverse effects*; D005901:Glaucoma / Q000601:surgery*; D006801:Humans; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D012449:Safety; D016212:Transforming Growth Factor beta / Q000276:immunology*
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen