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M.C. Kenney, N.C. Zorapapel, A.V. Ljubimov, S.R. Atilano, D.J. Brown; IGF-I as a Modulating Factor for Bullous Keratopathy Corneas . Invest. Ophthalmol. Vis. Sci. 2003;44(13):919.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Pseudophakic bullous keratopathy (PBK) is a leading indication for corneal transplantation. PBK corneas have increased levels of tenascin-C (TN-C), fibrillin-1 (Fib-1), matrix metalloproteinase-2 (MMP-2), infiltrating macrophages/inflammatory cells but lack myofibroblasts. Previous studies showed PBK corneas have increased levels of insulin-like growth factor-I (IGF-I), bone morphogenetic protein-4 (BMP-4) and transforming growth factor-ß (TGF-ß). The current study was conducted to determine whether any of these exogenous growth factors could elicit a PBK-like response from cells in vitro. Methods: Normal and PBK stromal keratocyte cultures were treated with IGF-I, BMP-4, or TGF-ß. Western blotting, Northern blotting, gelatinase zymography and activity assays were performed. Results: IGF-I increased the accumulation of TN-C protein, Fib-1 protein and RNA, MMPs (gelatinases inhibited by EDTA) and had no effect on α-SMA (marker for myofibroblasts). BMP-4 had no effect on TN-C, Fib-1 or α-SMA but increased MMPs. TGF-ß increased TN-C protein, Fib-1 protein and RNA, had little effect on MMPs but also induced α-SMA. Conclusions: Using an in vitro system, exogenous IGF-I most closely elicited responses similar to the parameters found in human PBK corneas, i.e., accumulations of TN-C, Fib-1, and MMPs all in absence of myofibroblasts. These data suggest that IGF-I may be the important modulating factor for this disorder. Support: NIH EY10836; Schoellerman Charitable Foundation; Discovery Fund for Eye Research; Skirball Foundation, and Guenther Foundation. NONE
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