Sonic hedgehog promotes stem-cell potential of Muller glia in the mammalian retina

Muller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regu- lated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Muller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Muller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Muller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rho- dopsin-positive photoreceptors from Muller glia-derived cells. Together, these results provide evidences that Muller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons. 2007 Elsevier Inc. All rights reserved.