| First Author | Nomura-Komoike K | Year | 2016 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
| Issue | 3 | Pages | 1169-82 |
| PubMed ID | 26975029 | Mgi Jnum | J:254648 |
| Mgi Id | MGI:6112102 | Doi | 10.1167/iovs.15-18101 |
| Citation | Nomura-Komoike K, et al. (2016) DNA Damage Response in Proliferating Muller Glia in the Mammalian Retina. Invest Ophthalmol Vis Sci 57(3):1169-82 |
| abstractText | PURPOSE: Muller glia, the principal glial cell type in the retina, have the potential to proliferate and regenerate neurons after retinal damage. However, unlike the situation in fish and birds, this capacity of Muller glia is extremely limited in mammals. To gain new insights into the mechanisms that hamper retinal regeneration in mammals, we examined the cell cycle progression and DNA damage response in Muller glia after retinal damage. METHODS: Expression of cell cycle-related proteins and DNA damage response were analyzed in adult rat and mouse retinas after N-methyl-N-nitrosourea (MNU)- or N-methyl-D-aspartate (NMDA)-induced retinal damage. Zebrafish and postnatal rat retinas were also investigated for comparison. Analysis was conducted by using immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction. RESULTS: In the rat retina, most Muller glia reentered the cell cycle after MNU-induced photoreceptor damage while no proliferative response was observed in the mouse model. Cell cycle reentry of rat Muller glia was accompanied by DNA damage response including the phosphorylation of the histone variant H2AX and upregulation of p53 and p21. The DNA damage response was also observed in rat Muller glia after NMDA-induced loss of inner retinal neurons, but not in zebrafish Muller glia or rat retinal progenitor cells. CONCLUSIONS: Our findings suggest that the DNA damage response induced by unscheduled cell cycle reentry may be one of the mechanisms that limit the proliferative and regenerative capacity of Muller glia in the mammalian retina. |
