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M. Francesca Cordeiro, Martin B. Reichel, Jennifer A. Gay, Fabiana D’Esposita, Robert A. Alexander, Peng T. Khaw; Transforming Growth Factor-β1, -β2, and -β3 In Vivo: Effects on Normal and Mitomycin C–Modulated Conjunctival Scarring. Invest. Ophthalmol. Vis. Sci. 1999;40(9):1975-1982.
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purpose. To compare the effects of the three human isoforms of transforming
growth factor (TGF)-β 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
methods. Application of recombinant human TGF-β was assessed in a prospective,
randomized study of mouse conjunctival scarring, in which
subconjunctival TGF-β1, -β2, and -β3 (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-β2
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-β behaved in a similar manner in vivo,
being associated with a rapid-onset and exaggerated scarring response
compared with control and MMC treatment. TGF-β–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-β2 treatment
significantly stimulated scarring after MMC application
(P < 0.05).
conclusions. TGF-β1, -β2, and -β3 appear to have similar actions in vivo and
stimulate the conjunctival scarring response. Application of TGF-β2
modified the effects of MMC. All TGF-β isoforms may be potent
modulators of the conjunctival scarring response. These studies
indicate that TGF-β2 may naturally modify the antiscarring effects of
antimetabolites such as MMC in glaucoma filtration
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