Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish
- Silva, N.J., Nagashima, M., Li, J., Kakuk-Atkins, L., Ashrafzadeh, M., Hyde, D.R., Hitchcock, P.F.
- Glia 68(7): 1445-1465 (Journal)
- Registered Authors
- Hitchcock, Peter, Hyde, David R., Kakuk-Atkins, Laura, Nagashima, Mikiko
- Müller glia, cytokines, immunosuppression, microglia, proliferation, stem cell
- MeSH Terms
- Animals, Genetically Modified
- Cell Differentiation/physiology
- Cell Proliferation/physiology
- Matrix Metalloproteinase 9/metabolism*
- Nerve Regeneration/physiology*
- Retinal Rod Photoreceptor Cells/physiology
- Stem Cells/physiology
- 32034934 Full text @ Glia
Silva, N.J., Nagashima, M., Li, J., Kakuk-Atkins, L., Ashrafzadeh, M., Hyde, D.R., Hitchcock, P.F. (2020) Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish. Glia. 68(7):1445-1465.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes