Inhibition of transforming growth factor-beta1 and its effects on human corneal fibroblasts by mannose-6-phosphate Potential for preventing haze after refractive surgery.
OBJECTIVE
To evaluate the action of mannose-6-phosphate (M6P) as an inhibitor of transforming growth factor-beta1 (TGF-beta1) and its effects on human corneal fibroblasts.


METHODS
Department of Academic Ophthalmology, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.


METHODS
Keratocytes were cultured in serum-containing medium with added TGF-beta1 and in serum-containing medium containing TGF-beta1 with M6P. Controls consisted of cells in serum-containing medium alone and cells cultured in serum-containing medium with M6P. Differentiation of fibroblasts into myofibroblasts was detected by immunohistochemistry for alpha-smooth muscle actin. Images were captured by laser confocal microscopy.


RESULTS
The differentiation of cells into myofibroblasts was significantly greater after culture in medium containing TGF-beta1 than in control cultures. Myofibroblast differentiation of cells was significantly reduced when cultured in medium containing TGF-beta1 with M6P (P<.001).


CONCLUSIONS
Mannose-6-phosphate significantly reduced TGF-beta1-mediated transformation of human corneal fibroblasts into myofibroblasts; it is a potential modulator of corneal wound healing and may reduce haze after refractive surgery.


BACKGROUND
Neither author has a financial or proprietary interest in any material or method mentioned.
Angunawela
Romesh I
RI
Department of Academic Ophthalmology, Rayne Institute, St Thomas' Hospital, London, United Kingdom. romeshi@hotmail.com
Marshall
John
J
D000199:Actins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology*; D003318:Corneal Opacity / Q000517:prevention & control*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008360:Mannosephosphates / Q000494:pharmacology*; D018613:Microscopy, Confocal; D011183:Postoperative Complications; D054140:Refractive Surgical Procedures; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000502:physiology
C541116:ACTA2 protein, human; D000199:Actins; D008360:Mannosephosphates; D053773:Transforming Growth Factor beta1; C027693:mannose-6-phosphate