Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish. Issue 7 (8th February 2020)

• Record Type: Journal Article
• Authors: Silva, Nicholas J.; Nagashima, Mikiko; Li, Jingling; Kakuk‐Atkins, Laura; Ashrafzadeh, Milad; Hyde, David R.; Hitchcock, Peter F.
• Is Part Of: Glia. Volume 68:Issue 7(2020)
• Page Start: 1445
• Page End: 1465
• Publication Date: 2020-02-08
• Subjects: cytokines -- immunosuppression -- microglia -- Müller glia -- proliferation -- stem cell; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23792
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the zebrafish retina and determine the cellular expression and function of the inflammatory protease, matrix metalloproteinase 9 (Mmp‐9), during this regenerative neurogenesis. Following photoreceptor ablation, anti‐inflammatory treatment suppresses the number of injury‐induced progenitors and regenerated photoreceptors. Upon photoreceptor injury, mmp‐9 is induced in Müller glia and Müller glia‐derived photoreceptor progenitors. Deleting mmp‐9 results in over production of injury‐induced progenitors and regenerated photoreceptors, but over time the absence of Mmp‐9 compromises the survival of the regenerated cones. At all time‐points studied, the levels of tnf‐α are significantly elevated in mutant retinas. Anti‐inflammatory treatment in mutants rescues the defects in cone survival. These data provide a link between injury‐induced inflammation in the vertebrate CNS, Mmp‐9 function during neuronal regeneration and the requirement of Mmp‐9 for the survival of regenerated cones. Abstract : Acute inflammation is necessary for photoreceptor regeneration in zebrafish. MMP‐9 negatively regulates Müller glia‐derived progenitors during photoreceptor regeneration. Mmp‐9 promotes the survival of regenerated cone photoreceptors.