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Human anti-transforming growth factor-beta2 antibody: a new glaucoma anti-scarring agent
M F Cordeiro1, J A Gay, P T Khaw
1Wound Healing Research Unit, Moorfields Eye Hospital and Institute of Ophthalmology, London, United Kingdom.
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)-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.
Insights
A new antibody targeting transforming growth factor (TGF)-beta2 shows promise as a safer anti-scarring agent for glaucoma surgery. This TGF-beta2 antibody effectively reduced conjunctival scarring in vitro and in vivo, improving surgical outcomes with good safety.
Area of Science:
- Ophthalmology
- Cell Biology
- Immunology
Background:
- Current anti-scarring treatments for glaucoma filtration surgery carry risks of blinding complications.
- There is a critical need for safer alternative agents to manage conjunctival scarring post-surgery.
Purpose of the Study:
- To investigate the efficacy of a novel antibody targeting transforming growth factor (TGF)-beta2 in reducing conjunctival scarring.
- To assess the safety and effectiveness of this antibody in glaucoma filtration surgery models.
Main Methods:
- Studied the activity of a recombinant monoclonal neutralizing antibody (mAb) to human TGF-beta2 (rhAnti-TGF-beta2 mAb) on conjunctival fibroblast proliferation, migration, and collagen contraction in vitro.
- Evaluated the safety of subconjunctival rhAnti-TGF-beta2 mAb administration in vivo.
- Assessed the antibody's effect on conjunctival scarring and surgical outcomes in a rabbit model of glaucoma filtration surgery.
Main Results:
- The rhAnti-TGF-beta2 mAb demonstrated potent inhibition of TGF-beta2-mediated conjunctival scarring in vitro (IC50 < 1 nM).
- Significantly improved glaucoma filtration surgery outcomes in an animal model compared to controls (P = 0.0291).
- Showed clinical safety, with no toxicity and good tolerability after subconjunctival administration.
Conclusions:
- Subconjunctival rhAnti-TGF-beta2 mAb treatment effectively reduces conjunctival scarring both in vitro and in vivo, positively impacting surgical outcomes.
- The antibody appears safe for subconjunctival use and is less destructive to local tissue than mitomycin-C.
- rhAnti-TGF-beta2 mAb holds potential as a novel anti-scarring agent for glaucoma filtration surgery.
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