[Potential for neural regeneration in the adult mammalian retina]

It has long been believed that the retina of mature mammals is incapable of regeneration. However, here we show that Müller glia of adult mammals could be progenitor cells, and generate new retinal neurons.

N-methyl-D-aspartate(NMDA) was injected into the vitreous chamber of adult rat (postnatal 6-7 weeks) eyes to induce neurotoxic injury. We injected bromo-deoxyuridine (BrdU) into the vitreous chamber and intraperitoneal space, and performed immunohistochemistry staining for BrdU and cell specific markers. To test whether exogenous growth factors stimulate proliferating cells, we injected retinoic acid into the vitreous chamber after NMDA treatment. We next misex-pressed basic helix-loop-helix (bHLH) and homeobox genes in NMDA-treated retinas using a retroviral expression system.

Müller glia of adult mammalian retinas proliferated in response to acute damage two days after NMDA treatment. These cells acquired a progenitor-like phenotype, and some of them migrated to the outer nuclear layer (ONL). A few of these cells expressed bipolar specific or rod photoreceptor specific markers. Retinoic acid treatment increased bipolar cell genesis. Misexpression of Math3 or NeuroD along with Pax6 promoted differentiation to amacrine cells. Co-expression of Crx and NeuroD promoted rod genesis.

These findings demonstrated that retinal neurons regenerated even in adult mammalian retinas after toxic injury. We could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes.