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L. Iyengar, B. Patkunanathan, J.W. McAvoy, F.J. Lovicu; Growth Factors Involved in Aqueous–Induced Lens Cell Proliferation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2404.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A number of different growth factors in the aqueous have been identified as mitogens for lens epithelial cells. These growth factors act through receptor tyrosine kinases which primarily signal through the MAPK/ERK and PI3–K pathways. The main aim of this study was to identify the specific growth factors in the aqueous important for regulating lens cell proliferation by selectively blocking specific growth factor signalling in aqueous–induced lens cell proliferation. Methods: Using the rat lens epithelial explant system, BrdU incorporation was used to compare the effects of aqueous, IGF–1, PDGF–A, EGF and FGF–2 on cell proliferation. Western blotting was also employed to characterise the signalling (ERK & Akt) profiles induced by these mitogens. In addition, the above assays were repeated in the presence of specific receptor inhibitors for IGF, PDGF, EGF and FGF. Results: Similar to aqueous, FGF induced a sustained signalling profile for up to 6 hours, unlike EGF which induced a sustained signalling profile for only 1 hour. In contrast, IGF and PDGF induced a transient activation of ERK which peaked at 20 mins. In the presence of a FGF receptor inhibitor, the sustained aqueous signalling profile was perturbed, now resembling an IGF or PDGF profile. In the presence of other growth factor receptor inhibitors (e.g. for IGF or PDGF), aqueous maintained its sustained 6 hour signalling profile, albeit the earlier stages of ERK activation were markedly reduced. No one specific receptor inhibitor was sufficient to block aqueous–induced lens cell proliferation, however, different combinations of inhibitors, providing one of these blocked FGFR signalling, abrogated aqueous–induced proliferation. Conclusions: Multiple mitogens are required for aqueous–induced lens cell proliferation. By characterising the role of individual growth factors within the aqueous, we hope to identify the specific mitogens and the signalling pathways involved in the tight regulation of lens cell proliferation in vivo.
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