Purchase this article with an account.
M. O. Karl, K. Tan, T. A. Reh; Loss of Amacrines Not Photoreceptors Stimulates Regeneration of Amacrines. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6454.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinal regeneration is well established in non-mammalian vertebrates. Recent reports have found that to a limited extent similar processes can be induced in adult rodent retina.
We examined regeneration in adult mice. To address this question in vivo we damaged adult mouse retina by intraocular injection of neurotoxin NMDA (loss of amacrine and retinal ganglion cells) or by light damage (loss of photoreceptor cells). Two days later we subsequently injected growths factors. Several growths factors were tested and animals were sacrificed at various time points. Retinas were analyzed using immunostaining.
Here we provide further evidence that Muller glia are the source for neural regeneration and we show that loss of retinal ganglion and amacrine cells, but not photoreceptors increases the number of regenerating amacrines. Muller glia express GFAP upon retinal injury. Using a genetic lineage trace we stimulated a population of GFAP expressing glia to proliferate and regenerate amacrines cells upon neurotoxic damage. Exposure to bright light leads to photoreceptor damage and subsequent injection of growth factors does not increase the number of regenerated GAD67-GFP neurons (amacrines, 44 +/-22 S.E.M. cells/retina; N=3) compared to growth factor injections alone (42 +/-16; N=3). In contrast, NMDA induced neurotoxic injury with subsequent growth factor stimulation led to a significant higher number of regenerated GAD67-GFP neurons (97 +/-5; N=6). None of the treatments we tested so far after retinal light or NMDA damage led to regeneration of photoreceptors (Nrl-GFP), bipolar (mGluR6-GFP) or retinal ganglion cells (Thy1-CFP) in adult mice in vivo.
Our results suggest that a restricted number of Muller glia may regenerate amacrines in living adult mice; this process is damage dependent in that loss of amacrines but not loss of photoreceptors promotes amacrine regeneration. We conclude that mechanisms to signal amacrine loss as a component of a retinal regenerative program exist and are in place while others are limited or absent.
This PDF is available to Subscribers Only