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I. Alcalde, G. Ferrara, S. del Olmo, M. Chacon, J. Merayo-Lloves; Changes in Phenotype of Neural-Like Corneal Stromal Cells During a Wound Healing Process. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6232.
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After injury, the keratocytes of the corneal stroma become reactive and transform to myofibroblasts wich proliferate to repair the damaged area. TGFβ1 induces this differentiation. Reinnervation of the injured cornea is promoted by the migration of Schwann cells from the limbus and by the transdifferentiation of a subpopulation of keratocytes to a neural-like phenotype. The aim of this study is to elucidate the evolution of a neural-like phenotype of corneal stromal cells involved in reinnervation and wound healing.
Fifteen mice were operated by PRK to obtain a model of corneal injury and wound healing process. Whole mounted corneas and transversal sections of the injured area were incubated with antibodies against TUJ1, S100, αSMA, TGFβ1 and erbB2 in order to demonstrate immunohistochemically the presence of these markers in the newly formed stromal tissue. RT-PCR analysis was performed in order to evaluate the time course of the expression of these markers.
In the first events of a wound healing process after PRK surgery, the newly formed tissue expresses high levels of TGFβ1 originating the transformation of keratocytes into myofibroblasts, as demonstrated by their immunoreactivity against αSMA. In addition to Schwann cells supporting effect in axonal regeneration, a subpopulation of keratocytes exhibit an intermediate phenotype presenting both myofibroblast and glial markers such as S100 calcium binding protein or erbB2 tyrosine kinase receptor. The expression of erbB2 is related to the delivery of neural growth factors that may induce the transformation of keratocytes into a neural-like phenotype.
Neural elements of the corneal stroma exert a potent effect over stromal cells and regulate their phenotype to improve reinnervation and wound healing.Combination of TGFβ1 and some factors derived from axons could promote the wound healing process.
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