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.

Abstract

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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