Abstract
Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5+ cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5+ amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5+ amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5+ amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.
Highlights
The mammalian retina is a well-characterized structure consisting of six types of neurons and one type of glia
To assess whether leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is expressed in the mouse retina, we examined the expression of the Lgr5 gene in the retina of Lgr5EGFP-Ires-CreERT2 knock-in mice, which express EGFP and the inducible Cre recombinase bi-cistronically from the endogenous Lgr5 locus (Barker et al, 2007)
We found that EGFP expressed from this locus was detected in the adult mouse retina and limited to a population of cells within the inner half of the inner nuclear layer (Fig. 1A)
Summary
The mammalian retina is a well-characterized structure consisting of six types of neurons and one type of glia. The ciliary marginal zone is greatly reduced in birds and absent in mammals, consistent with the limited avian retinal proliferative capacity and the presumed absence of neurogenesis in the retina of adult mammals (Kubota et al, 2002). This absence of regeneration is thought to contribute to a host of retinal degenerative diseases, including age-related macular degeneration, glaucoma and retinitis pigmentosa, which have been viewed as consequences of the irreversible loss of retinal neurons (Rattner & Nathans, 2006; Bhatia et al, 2010; Moore & Goldberg, 2010; Wohl et al, 2012)
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