PUBLICATION
Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system
- Authors
- Lemmens, K., Bollaerts, I., Bhumika, S., De Groef, L., Van Houcke, J., Darras, V.M., Van Hove, I., Moons, L.
- ID
- ZDB-PUB-151029-2
- 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.
Citation
Lemmens, K., Bollaerts, I., Bhumika, S., De Groef, L., Van Houcke, J., Darras, V.M., Van Hove, I., Moons, L. (2016) Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system. The Journal of comparative neurology. 524(7):1472-93.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping