Abstract bekijken

Deze abstract is toegekend aan sessie Poster session
TitelPharmacological matrix metalloproteinase (MMP) inhibition blocks axonal regeneration in the damaged retinotectal system of the adult zebrafish
Abstract Nr.1048
DoelComplete restoration of the injured mammalian central nervous system (CNS) remains a challenge, making the search for regenerative molecules essential. Matrix metalloproteinases (MMPs), (non)-matrix protein cleaving endopeptidases, are upregulated during CNS repair, reduce glial scar formation and potentially promote axonal regrowth. As such MMPs or their underlying molecules likely form potent regenerative molecules. One study already reported upregulated mRNA levels of specific MMPs in spontaneously regenerating eyes of adult zebrafish subjected to an optic nerve crush (ONC). Here, we intend to elucidate the role of these MMPs in zebrafish retinotectal regeneration.
MethodesImmunohistochemistry and Western blotting were used to determine the protein expression pattern of MMP-2,-9,-13a and -14 after ONC in the regenerating zebrafish retina. To investigate the role of MMPs in retinal ganglion cell (RGC) axonal regeneration, a broad-spectrum (GM6001) inhibitor was intravitreally injected at specific time points after ONC. Biocytin labeling was used to study tectal reinnervation.
ResultatenOur expression data show a spatiotemporal expression of these MMPs in the regenerating zebrafish retina and suggest an individual role in RGC survival, axonal regrowth and dendritic/synaptic remodeling. Moreover, broad-spectrum MMP inhibition during the first week after ONC significantly reduces retinotectal regeneration without influencing RGC survival.
ConclusieOur study reveals that MMPs are associated with zebrafish retinotectal regeneration and that these enzymes or their downstream targets might be of therapeutic value for the injured mammalian CNS.
Auteur 1
NaamLEMMENS
InitialenKim
InstituutBiology
StadLeuven
Auteur 2
NaamBollaerts
InitialenI
InstituutBiology
Stadleuven
Auteur 3
NaamBhumika
InitialenS
InstituutBiology
StadLeuven
Auteur 4
NaamVan houcke
InitialenJ
InstituutBiology
StadLeuven
Auteur 5
NaamVan Hove
InitialenI
InstituutBiology
StadLeuven
Auteur 6
NaamMoons
InitialenL
InstituutBiology
StadLeuven
top ^