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1: Brain Res Bull. 2006 Dec 11;71(1-3):208-18. Epub 2006 Oct 2.

The growth factor response in ischemic rat retina and superior colliculus after
brimonidine pre-treatment.

Lönngren U, Näpänkangas U, Lafuente M, Mayor S, Lindqvist N, Vidal-Sanz M,
Hallböök F.

Department of Neuroscience, Uppsala University, Uppsala, Sweden.

The alpha-2-adrenergic receptor agonist brimonidine has been shown to increase
survival of retinal ganglion cells following ischemic injury to the rat retina.
Increased expression of growth factors has been suggested to be involved in this 
action. We investigated expressional changes of growth factors and their
receptors following transient retinal ischemia induced by selective ligature of
ophthalmic vessels in rats pre-treated with vehicle or 0.5% brimonidine. In
addition, analysis of expression in retinal samples following unilateral
administration of brimonidine to normal tissue was performed. Tissue samples of
retina and superior colliculus were collected at time points between 6h and 14
days of retinal reperfusion. Analysis of mRNA levels of the ligands BDNF, NT3,
CNTF, FGF1, FGF2, FGF9 and HGF; as well as the receptors TrkB, TrkC, p75(NTR),
CNTFRalpha, FGFR1, FGFR3, FGFR4 and HGFR were performed using qRT-PCR. The cell
specific markers Thy1 and GFAP were analysed. We report transiently increased
retinal levels of BDNF, NT3, p75(NTR), FGFR1 and HGFR and decreased levels of
FGF9, HGF, TrkB, TrkC, FGFR4 and Thy1 following ischemia. The decreases were
counteracted by brimonidine. Brimonidine treatment gave an increase in BDNF, NT3 
and CNTF levels compared to the vehicle treated group. In superior colliculus
increased levels of growth factor mRNA were found. In conclusion, transient
ischemia has a profound effect on gene expression in rat retina. Alterations can 
also be seen in the superior colliculus but are smaller. Brimonidine
pre-treatment attenuates an acute injury-induced response by decreasing the
expression of several genes, among them p75(NTR). Brimonidine also causes a
prolonged increase of several growth factors as well as receptors in retina and
superior colliculus compared to the ischemic situation. The increased expression 
of several growth factors represents a coordinated growth factor system response 
that differs from the ischemia-induced changes and is likely part of the
neuroprotective activity that is elicited by BMD pre-treatment.

PMID: 17113948 [PubMed - indexed for MEDLINE]

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