Reactive gliosis in the adult zebrafish retina

Abstract

In contrast to mammals, zebrafish posses the remarkable ability to regenerate retinal neurons. Damage to the zebrafish retina induces Müller glia to act as stem cells, generating retinal progenitors for regeneration. In contrast, injury in the mammalian retina results in Müller glial reactive gliosis, a characteristic gliotic response that is normally detrimental to vision. Understanding the signaling pathways that determine how Müller glia respond to injury is a critical step toward promoting regeneration in the mammalian retina. Here we report that zebrafish Müller glia exhibit signs of reactive gliosis even under normal regenerative conditions and that cell cycle inhibition increases this response. Persistently reactive Müller glia increase their neuroprotective functions, temporarily saving photoreceptors from a cytotoxic light lesion. However, the absence of a sustained proliferation response results in a significant inhibition of retinal regeneration. Interestingly, when cell cycle inhibition is released, a partial recovery of regeneration is observed. Together, these data demonstrate that zebrafish Müller glia possess both gliotic and regenerative potential.

Keywords: 5-Fluorouracil; Müller glia; Ouabain; Photoreceptor; Regeneration.