Regeneration of retinal neurons and glia by Lgr5⁺ amacrine cells in adult mice

Abstract

Purpose: Retinal cells that possess the capacity to regenerate lost neurons hold great therapeutic potential for vision restoration in people who suffer from blindness associated with retinal degeneration. The purpose of this study is to identify adult mammalian retinal cells that have regenerative capacity.

Methods: To identify these cells, we adapted a genetic strategy. We first examined the expression of the adult stem cell marker, leucine rich repeat containing G-protein coupled receptor 5 (Lgr5), in the retina of the Lgr5^{EGFP-Ires-CreERT2} mice, and determined the identity of Lg5⁺ cells with established retinal cell markers. We then labeled Lgr5⁺ cells with the Rosa26-LacZ reporter in the Lgr5^{EGFP-Ires-CreERT2}; Rosa26-LacZ mice, and further determined if new retinal cells could be generated from labeled cell at later times.

Results: We observed that Lgr5 was expressed in the inner nuclear layer of the retina and marked a population of amacrine cells in adult mice. Nevertheless, LacZ⁺ retinal cells could be detected at later times in new locations, including the ganglion cell layer under physiological condition and the photoreceptor layer in response to injury.

Conclusions: These findings suggest that Lgr5⁺ amacrine cells may function as an endogenous regenerative source and contribute to retinal homeostatic maintenance. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and points to therapeutic opportunities for debilitating retinal diseases.