Inhibition of GABA Initiates Retina Regeneration in the Zebrafish

Abstract

Retina damage or disease in humans often leads to reactive gliosis, preventing the formation of new cells and resulting in visual impairment or blindness. Currently, treatments are being developed to stimulate repair or replacement of lost retinal neurons by intravitreal injection of stem cells or retina precursors. Though improving, these therapies are inefficient and not yet capable of fully restoring vision. In contrast to mammals, the zebrafish retina is capable of spontaneous regeneration upon damage, using Müller glia (MG) derived progenitors. Understanding how zebrafish MG initiate regeneration may allow for the discovery of treatments that prompt mammalian retinas to regenerate. Here I show that inhibition of GABA signaling facilitates MG proliferation and initiation of retina regeneration. Using pharmacological and genetic approaches to disrupt neurotransmitter signaling, I demonstrate that GABAA receptor inhibition stimulates spontaneous regeneration in undamaged zebrafish retinas while GABAA receptor activation inhibits regeneration in damaged zebrafish retinas. This is the first evidence that neurotransmitters control retina regeneration in zebrafish through an evolutionarily conserved mechanism of neurogenesis.