Proliferation Potential of Muller Glia after Retinal Damage Varies between Mouse Strains

Retinal Muller glia can serve as a source for regeneration of damaged retinal neurons in fish, birds and mammals. However, the proliferation rate of Muller glia has been reported to below in the mammalian retina. To overcome this problem, growth factors and morphogens have been studied as potent promoters of Muller glial proliferation, but the molecular mechanisms that limit the proliferation of Muller glia in the mammalian retina remain unknown. In the present study, we found that the degree of damage-induced Muller glia proliferation varies across mouse strains. In mouse line 129 x 1/SvJ (129), there was a significantly larger proliferative response compared with that observed in C57BL/6 (B6) after photoreceptor cell death. Treatment with a Glycogen synthase kinase 3 (GSK3) inhibitor enhanced the proliferation of Muller glia in 129 but not in B6 mouse retinas. We therefore focused on the different gene expression patterns during retinal degeneration between B6 and 129. Expression levels of Cyclin D1 and Nestin correlated with the degree of Muller glial proliferation. A comparison of genome-wide gene expression between B6 and 129 showed that distinct sets of genes were upregulated in the retinas after damage, including immune response genes and chromatin remodeling factors.