Purchase this article with an account.
L.W. Reneker, L. Xie; Sprouty Proteins Function as Negative Regulators in Lens Cell Proliferation and Lens Development . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2406.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Growth factor activated receptor tyrosine kinases (RTKs) play important roles in lens cell proliferation and differentiation. Sprouty (Spry) proteins have been identified as negative regulators of the RTK–signaling. The purpose of this study is to examine whether Spry genes are expressed in the mouse lens during development and to investigate the role of Spry2 in lens development in transgenic mice. Methods: Expression of Spry1, 2 and 4 in the lens was examined by in situ hybridization. Transgenic mice expressing Spry2 in the lens were generated using the heterogenic promoter containing the Δ1–crystallin enhancer linked to the mouse αA–crystallin promoter. Changes in cell proliferation, differentiation and survival in the lenses of the Spry2 transgenic mice were analyzed by histology, immunohistochemistry and in situ hybridization. Results: During lens development, Spry1 and 2 are expressed in the lens epithelium and differentiating fiber cells. Overexpression of Spry2 in the lens of transgenic mice resulted in a significant inhibition of lens growth. In the two established lines, all the transgenic mice developed microphthalmia. Bromodeoxyuridine (BrdU) incorporation assay showed that cell proliferation was significantly inhibited in the Spry2 transgenic lenses. In the transgenic line with a higher transgene expression level, apoptosis occurred in the lens fiber cells. Spry2 overexpression did not seem to inhibit fiber cell differentiation in the lens of the transgenic mice, as determined by immunohistochemical staining for ß– and γ–crystallins. Conclusions: Expression of Spry1 and 2 in the lens during normal development suggests that lens cell proliferation and differentiation could be tightly regulated by both positive and negative signals. The data from the Spry2 transgenic mice imply that Spry2 functions as an antagonist to inhibit lens cell proliferation during development.
This PDF is available to Subscribers Only