Inflammation modulates regeneration in the acute or chronically damaged zebrafish retina

Abstract

Unlike mammals, zebrafish regenerate in response to retinal damage. Because microglia are activated by retinal damage, we investigated their role during regeneration following acute or chronic damage. At three weeks-post-fertilization (wpf), fish exhibiting NMDA-induced acute damage or cone photoreceptor-specific chronic degeneration, the gold rush (gosh) mutant, displayed reactive microglia and Muller glia proliferation. Retinas treated to inhibit the immune response lacked reactive microglia and possessed fewer PCNA-positive cells, while LPS treatment increased microglia and PCNA-labeled cells. NMDA-injured retinas upregulated the expression of il-1{beta} and tnf- pro-inflammatory cytokine genes, followed by increased expression of il-10 and arg1 anti-inflammatory/remodeling cytokine genes. An early and transiently TNF- pro-inflammatory microglia population was identified in the NMDA-damaged retina. In contrast, gosh mutant retinas exhibited a mild increase of pro-inflammatory cytokine gene expression concurrently with a greater increased in anti-inflammatory/remodeling cytokine gene expression. Few TNF- pro-inflammatory microglia were observed in the gosh retina. How inflammation regulates regeneration in zebrafish would provide important clues towards improving the therapeutic strategies for repairing injured mammalian tissues.