Abstract
Purpose:
One of the signaling pathways that may regulate the activity of retinal glia and Müller glia-derived progenitor cells (MGPCs) is the Wnt pathway. During ocular development, Wnt-signaling is known to have many important functions that involve patterning the anterior optic structures and suppressing retinal development. Studies in zebrafish have shown that activation of Wnt-signaling is required for MGPC-mediated retinal regeneration in vivo. Studies in mammalian retina have shown that Wnt-signaling stimulates the Müller glia to re-enter the cell cycle in retinal explants in vitro. We investigate the role of the Wnt pathway in the formation of MGPCs in the avian retina in vivo.
Methods:
: Immunocytochemistry was used to study the expression pattern of nuclear β-catenin (a read-out of Wnt-signaling) in mature and damaged chick retinas. Wnt- signaling inhibitors (XAV939) or a combination of Wnt-signaling activators (GSK3β-inhibitors) were injected into the vitreous chamber of normal and damaged eyes. Retinas were processed for cell proliferation and glial reactivity. qRT-PCR was used to measure retinal levels of different Wnt-related and progenitor genes. Retinal damage was induced by an intraocular injection of N-Methyl-D-aspartate (NMDA).
Results:
We found that nuclear β-catenin is present in many neurons, but not Müller glia in mature retina. In damaged retina nuclear β-catenin is expressed by MGPCs (need confirmation). Furthermore, NMDA-induced retinal damage leads to activation of Wnt-signaling, indicated by the regulation of transcripts of Wnt-target genes. Inhibition of Wnt-signaling suppressed the formation of proliferating MGPCs, and activation of Wnt-signaling expanded the population of the proliferating MGPCs.
Conclusions:
We propose that Wnt-signaling is important for the proliferation of MGPCs in damaged avian retina in vivo. Our data suggest a role of Wnt-signaling in the regeneration of the chick retina.
Keywords: 603 Muller cells •
699 retinal glia •
687 regeneration