Purchase this article with an account.
Y. Wang, V.A. Wallace; The Role of Hedgehog Pathway Activation on Proliferation and Diversification of Retinal Stem Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3239.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: The current treatment strategies for degenerative diseases of the retina, such as macular degeneration, retinitis pigmentosa and glaucoma, are limited and not curative. Hence there is widespread interest in the development of cell–based therapies to replace lost neurons in these diseases. Retinal stem cells (RSCs) can be isolated from the pigmented cells of the mouse and human adult ciliary margin, propagated as spheres in culture and can differentiate into retinal cell types, including photoreceptors. The signaling networks that regulate RSC self–renewal, as well as cell diversification, are not known. Since the morphogen Sonic hedgehog (Shh) plays an important role in regulating proliferation and differentiation in the developing retina, we addressed whether Hedgehog (Hh) pathway activation also plays a role in RSC behaviour. Methods: RSCs were isolated from wildtype adult mice and their response to Hh pathway activation was assessed. To address whether Shh signaling normally influences RSC development in vivo, we generated RSC–derived spheres from adult mice with a conditional mutation of the Shh gene in the peripheral retina (αCre;Shh–/c). Results: We did not find evidence for endogenous Hh pathway activation in RSC–derived spheres cultured under normal growth conditions. However, addition of an exogenous Hh pathway agonist to RSC sphere cultures resulted in an upregulated of Hh target gene activation and increased sphere number. RSC spheres from αCre;Shh–/c mice were smaller and reduced in number compared with cultures that were established from control littermates. Conclusions: Our findings indicate that Hh pathway activation may play a role in the development and/or maintenance of RSCs in vivo and that retinal neurospheres are responsive to Hh signals. In future studies, we will address whether activation of the Hh pathway might be a useful strategy for the in vitro expansion of RSCs.
This PDF is available to Subscribers Only