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1 From the Wound Healing Research and Glaucoma Units, Department of Pathology, Moorfields Eye Hospital and Institute of Ophthalmology; the 2 Department of Molecular Genetics, Institute of Ophthalmology, London, United Kingdom; and the 3 University of Florida, Gainesville.
Abstract
PURPOSE. To compare the effects of the three human isoforms of transforming growth factor (TGF)-ß in vivo using a mouse model of conjunctival scarring, both in normal eyes and after treatment with MMC, with a view to delineating the role of this growth factor in glaucoma filtration surgery.
METHODS. Application of recombinant human TGF-ß was assessed in a prospective, randomized study of mouse conjunctival scarring, in which subconjunctival TGF-ß1, -ß2, and -ß3 (all 10-9 M) were compared with control (phosphate-buffered saline [PBS] carrier) and mitomycin C (MMC; 0.4 mg/ml) treatment at 6 hours, and 1, 3, and 7 days after surgery (six eyes/treatment/time point). Effects of TGF-ß2 on eyes previously treated with MMC were also assessed. Histologic studies of enucleated eyes were performed to analyze development of the scarring response, extracellular matrix deposition, and the inflammatory cell profile.
RESULTS. All three isoforms of TGF-ß behaved in a similar manner in vivo, being associated with a rapid-onset and exaggerated scarring response compared with control and MMC treatment. TGF-ß–treated eyes showed evidence of an earlier peak in inflammatory cell activity (P < 0.05) and increased collagen type III deposition (P < 0.05). TGF-ß2 treatment significantly stimulated scarring after MMC application (P < 0.05).
CONCLUSIONS. TGF-ß1, -ß2, and -ß3 appear to have similar actions in vivo and stimulate the conjunctival scarring response. Application of TGF-ß2 modified the effects of MMC. All TGF-ß isoforms may be potent modulators of the conjunctival scarring response. These studies indicate that TGF-ß2 may naturally modify the antiscarring effects of antimetabolites such as MMC in glaucoma filtration surgery.
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