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L.W. Reneker, L. Xie; Ras-Signaling Is Required for Lens Growth and Development . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3256.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Expressing a dominant negative mutant of Ras (DN-Ras) in transgenic lens results in a smaller lens, suggesting that Ras activation is important for normal lens development. In this study, we investigated the role of Ras in lens cell proliferation, differentiation and survival. Methods: Cell proliferation was monitored by bromo-deoxyuridine (BrdU) incorporation and cyclin expression. Cell differentiation was examined by expression of fiber cell specific markers, including ß- and γ-crystallins, CP49 and filensin, and MIP. TUNNEL assay was used to identify apoptotic cells in the lens. Results: BrdU incorporation assay revealed a two-fold reduction in the number of S-phase cells in the DN-Ras transgenic lens. The cyclinD2 expression level was significantly downregulated in the epithelial cells of the DN-Ras transgenic lens, confirming the hypothesis that Ras activity is critical for lens cell proliferation. Fiber cell differentiation occurs but significantly delayed in the DN-Ras transgenic lens, as monitored by the expression of fiber cell specific proteins including ß- and γ-crystallins, CP49 and filensin, and MIP. This result suggests that Ras-signaling is also involved in fiber cell differentiation. TUNEL-positive cells can be identified in both epithelial and fiber cells of the DN-Ras transgenic lens. Conclusions: Ras activity is required for cell proliferation, differentiation and survival during normal lens development. It is possible that Ras plays a key role in the FGF receptor-activated signal transduction pathways.
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