Interneuron regeneration after ouabain treatment in the adult mammalian retina

The mammalian retina has the potential to regenerate rod cells, bipolar cells, and amacrine cells in vivo to repair damaged nervous tissue through the Müller glial cell (MGC)-mediated response. Both horizontal cell (HC) and amacrine cell are interneurons in the inner nuclear layer (INL) and are generated under the control of some common transcription factors during retinal development. However, to date, the ability of HC regeneration in vivo in mammals remains unclear. Here, ouabain (a Na/K-ATPase inhibitor) was injected into rat eyes to induce an obvious cell loss in the INL. The proliferation, dedifferentiation of MGC and production of new neurons after ouabain injection were examined by BrdU incorporation and immunohistochemistry. Our results showed that 2 days after ouabain treatment, MGCs incorporated BrdU and upregulated the expression of Nestin, which is a marker for retinal progenitor cells. Several weeks after ouabain injection, the BrdU-positive cells in the outer border of the INL expressed Prox1 and Calbindin D-28k, which are specific markers for HC. Taken together, these results suggest that the mammalian retina can regenerate new type of interneurons (HC) in vivo, which advances our understanding of mammalian retinal regeneration after damage.