Matrix metalloproteinase-9 is involved in the development and plasticity of retinotectal projections in rats.
OBJECTIVE
During postnatal development, retinotectal projections undergo a process of misplaced axon elimination, leading to a topographical matching between the retinal surface and the superior colliculus. Matrix metalloproteinases (MMPs) have been implicated in the development and plasticity of the nervous system. We studied the expression and role of MMPs during normal development of retinotectal projections and after monocular enucleation-induced plasticity.


METHODS
Lister hooded rats at different postnatal ages received subpial ethylene vinyl acetate 40W implants to deliver an MMP inhibitor or vehicle to the superior colliculus. Animals received intraocular injections of horseradish peroxidase for anterograde tracing of ipsilateral projections. For immunoblotting and zymography, colliculi were removed without fixation.


RESULTS
We observed the highest MMP activity in the first postnatal week, with decreasing activity thereafter. Monocular enucleation at postnatal day 10 yielded a rapid increase in MMP activity, 24 h following denervation of the contralateral colliculus. Importantly, inhibition of MMP activity in vivo induced a marked delay of axonal clustering along the medial aspect of colliculus.


CONCLUSIONS
Our data indicate that MMPs are crucial in retinotectal development concurring to the fine tuning of topographical order and synaptic specificity of these connections.
Oliveira-Silva
Priscilla
P
Neuroimmunology Program, Fluminense Federal University, Niterói, Brazil. priscillaneuro@gmail.com
Jurgilas
Patricia B
PB
Trindade
Pablo
P
Campello-Costa
Paula
P
Perales
Jonas
J
Savino
Wilson
W
Serfaty
Claudio A
CA
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000201:enzymology / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015353:Eye Enucleation; D007839:Functional Laterality / Q000502:physiology; D006735:Horseradish Peroxidase; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009473:Neuronal Plasticity / Q000502:physiology*; D011145:Polyvinyls / Q000494:pharmacology; D051381:Rats; D012160:Retina / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000201:enzymology; D013194:Staining and Labeling; D013477:Superior Colliculi / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D014795:Visual Pathways / Q000166:cytology / Q000201:enzymology / Q000254:growth & development
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D006735:Horseradish Peroxidase; D020780:Matrix Metalloproteinase 9