ZFIN ID: ZDB-PUB-151029-2
Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system
Lemmens, K., Bollaerts, I., Bhumika, S., De Groef, L., Van Houcke, J., Darras, V.M., Van Hove, I., Moons, L.
Date: 2016
Source: The Journal of comparative neurology   524(7): 1472-93 (Journal)
Registered Authors: Darras, Veerle
Keywords: AB_1565437, AB_1657437, AB_2069697, AB_2144746, AB_477171, AB_477593, AB_528480, AB_627659, AB_881233, AB_91192, MMP inhibitor studies, optic nerve crush, regeneration, retina, spatiotemporal expression pattern
MeSH Terms:
  • Analysis of Variance
  • Animals
  • Dipeptides/pharmacology
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic/drug effects
  • Gene Expression Regulation, Enzymologic/physiology*
  • Matrix Metalloproteinase Inhibitors/pharmacology
  • Matrix Metalloproteinases
  • Nerve Crush/methods
  • Nerve Regeneration/drug effects
  • Nerve Regeneration/physiology*
  • Neuronal Outgrowth/drug effects
  • Neuronal Outgrowth/physiology*
  • Optic Nerve Diseases/enzymology*
  • Optic Nerve Diseases/pathology
  • Tubulin/metabolism
  • Visual Pathways/pathology*
  • Zebrafish
PubMed: 26509469 Full text @ J. Comp. Neurol.
Overcoming the failure of axon regeneration in the mammalian central nervous system (CNS) after injury remains a major challenge, which makes the search for pro-regenerative molecules essential. Matrix metalloproteinases (MMPs) have been implicated in axonal outgrowth during CNS development and show increased expression levels during vertebrate CNS repair. In mammals, MMPs are believed to alter the suppressive extracellular matrix to become more permissive for axon regrowth. We investigated the role of MMPs in axonal regeneration following optic nerve crush (ONC) in adult zebrafish, which fully recover from such injuries due to a high intrinsic axon growth capacity and a less inhibitory environment. Lowering general retinal MMP activity through intravitreal injections of GM6001 after ONC strongly reduced retinal ganglion cell (RGC) axonal regrowth, without influencing RGC survival. Based on a recently performed transcriptome profiling study, the expression pattern of four MMPs after ONC was determined via combined use of Western blotting and immunostainings. Mmp-2 and -13a were increasingly present in RGC somata during axonal regrowth. Moreover, Mmp-2 and -9 became upregulated in regrowing RGC axons and inner plexiform layer (IPL) synapses respectively. In contrast, after an initial rise in IPL neurites and RGC axons during the injury response, Mmp-14 expression decreased during regeneration. Altogether, a phase dependent expression pattern for each specific MMP was observed, implying them in axonal regrowth and inner retina remodeling after injury. In conclusion, these data suggest a novel, neuron intrinsic, function for multiple MMPs in axon regrowth that is distinct from breaking down environmental barriers. This article is protected by copyright. All rights reserved.