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M. Matsuba, A. E. K. Hutcheon, J. D. Zieske; The Role of Thrombospondin-1 in Rat Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2964. doi: https://doi.org/.
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Recent studies have indicated that thrombospondin-1 (TSP-1) can activate the latent complex of transforming growth factor-β (TGF-β). TGF-β has been shown to play a major role in stimulating mesenchymal cells to synthesize extra-cellular matrix. After corneal injury, keratocytes become active and transform into corneal fibroblasts or myofibroblasts. It is our purpose to determine if TSP-1 regulates the transformation of keratocytes into myofibroblasts (MF) via TGF-β. In this study, we investigated the expression of TSP-1 and α-smooth muscle actin (α-SMA), a marker of MF, in a superficial keratectomy wound model.
A 3-mm superficial keratectomy wound was made in central rat corneas and allowed to heal 8 hours to 2 weeks in vivo. Unwounded normal eyes served as controls. Expression of TSP-1, Ki67 and α-SMA was examined by indirect immunofluorescence microscopy.
In unwounded corneas, TSP-1 expression was observed primarily in the endothelium, Ki67 was localized in the epithelial basal cells and no α-SMA was present in the central cornea. By 48 hours, TSP-1 expression appeared in the wounded stroma immediately subjacent to the wound-healing epithelium, and Ki67 was present in the stromal cells peripheral to the wound area. However, α-SMA-expressing cells were not observed in the wound area until 3-4 days after wounding. When they were observed, they were within the same area that TSP-1 was localized. At 1 week, the expression of α-SMA and TSP-1 appeared to peak. This expression seemed to decrease by 2 weeks. There was no apparent correlation between the expression of Ki67 and either TSP-1 or α-SMA. The expression of myofibroblasts in the wounded stroma was confirmed by electron microscopy.
TSP-1 may play a key role during corneal stromal repair by inducing myofibroblast generation. In our future studies, we will examine the correlation between TSP-1, TGF-β and α-SMA by immunoblotting, and will focus on determining which cells express TSP-1.
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