Abstract
Müller glia (MG) in the zebrafish retina respond to retinal injury by generating multipotent progenitors for retinal repair. Here, we show that Insulin, Igf-1, and fibroblast growth factor (FGF) signaling components are necessary for retina regeneration. Interestingly, these factors synergize with each other and with heparin-binding EGF-like growth factor (HB-EGF) and cytokines to stimulate MG to generate multipotent progenitors in the uninjured retina. These factors act by stimulating a core set of signaling cascades (Mapk/Erk, phosphatidylinositol 3-kinase [PI3K], β-catenin, and pStat3) that are also shared with retinal injury and exhibit a remarkable amount of crosstalk. Our studies suggest that MG both produce and respond to factors that stimulate MG reprogramming and proliferation following retinal injury. The identification of a core set of regeneration-associated signaling pathways required for MG reprogramming not only furthers our understanding of retina regeneration in fish but also suggests targets for enhancing regeneration in mammals.
Highlights
Vision is one of our most precious senses
To determine if Insulin signaling contributed to retina regeneration we investigated if Insulin signaling components were expressed in injury-responsive Müller glia (MG) and regulated during retina regeneration
We found that ins mRNA was induced in BrdU+ MG-derived progenitors following retinal injury (Figures 1A–1C)
Summary
Vision is one of our most precious senses. Many blinding eye diseases result from degenerating retinal neurons. Identifying strategies for regenerating these lost neurons may help restore lost sight. Mammals are unable to regenerate a damaged retina. Teleost fish, like zebrafish exhibit a remarkable regenerative ability that can restore sight to a damaged retina (Lindsey and Powers, 2007; Mensinger and Powers, 1999; Sherpa et al, 2008). Understanding the mechanisms by which zebrafish can regenerate a damaged retina may suggest strategies for stimulating retina regeneration in mammals
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