Age-related degeneration leads to gliosis but not regeneration in the zebrafish retina

Ageing is a significant risk factor for degeneration of the retina. Harnessing the regenerative potential of Müller glia cells (MG) in the retina offers great promise for the treatment of blinding conditions, such as age-related macular degeneration. Yet, the impact of ageing on their regenerative capacity has not yet been considered. Here we show that MG retain their ability regenerate after acute damage in the aged zebrafish retina. Despite this, we observe chronic age-related neurodegeneration in the retina, which is insufficient to stimulate MG proliferation and regeneration. Instead of regeneration, ageing leads to a gliotic response and loss of vision, recapitulating hallmarks of human retinal degeneration with age. Therefore we identify key differences in the MG regenerative response to acute versus chronic damage, a key consideration for stimulating endogenous regenerative mechanisms to treat human retinal disease.