Investigating the Role of Microglia in Retinal Regeneration of the Adult Zebrafish Retina

The zebrafish possesses a remarkable ability to regenerate dying retinal neurons in response to retinal injury. Both microglia and Müller glia play integral roles in this regenerative process. Resident Müller glia respond to damage by reprogramming and undergoing asymmetric cell division to generate neuronal progenitor cells. These progenitor cells continue to proliferate and differentiate into the lost neurons. In contrast, microglia become reactive, phagocytose dying cells, and release inflammatory signals into the surrounding tissue following damage. In recent years, there has been heightened attention in elucidating the intricate interplay between retinal regeneration and the immune system. Here I demonstrate that microglia become reactive and phagocytose dying photoreceptors following light damage. I also show that chemokines and inflammatory cytokines are differentially expressed during retinal regeneration, where the expression of a subset of pro-inflammatory cytokine genes is upregulated shortly after light damage and the expression of a subset of anti-inflammatory cytokine
genes is delayed before increasing their expression. Both pro-inflammatory cytokine IL- 1ß and anti-inflammatory cytokine IL-10 are essential for Müller glia proliferation in the light-damaged retinas. The absence of either IL-1ß or IL-10 results in fewer PCNA+ Müller glia in the damaged retinas. However, IL-1ß is sufficient to induce Müller glia proliferation in the undamaged retinas. While IL-10 is unable to induce Müller glia proliferation in undamaged retinas, it induces the Müller glia to adopt a gliotic cell morphology and expression of several gliotic genes. Together, these findings demonstrate the essential role of inflammatory cytokines IL-1ß and IL-10 in regeneration in the adult zebrafish retina.