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

• Published in: Brain research bulletin 2006-12, Vol.71 (1), p.208-218
• Main Authors: Lönngren, Ulrika, Näpänkangas, Ulla, Lafuente, Maria, Mayor, Sergio, Lindqvist, Niclas, Vidal-Sanz, Manuel, Hallböök, Finn
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists - pharmacology; Animals; Axons - drug effects; Axons - metabolism; Axons - pathology; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Brimonidine Tartrate; Cytoprotection - drug effects; Cytoprotection - physiology; Disease Models, Animal; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Injury; Intercellular Signaling Peptides and Proteins - genetics; Male; MEDICIN; MEDICINE; Nerve Degeneration - drug therapy; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Neuroprotective Agents - pharmacology; Neurotrophic factor; Optic Nerve - drug effects; Optic Nerve - metabolism; Optic Nerve - pathology; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Real time PCR; Receptors, Adrenergic, alpha-2 - metabolism; Receptors, Growth Factor - genetics; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Superior Colliculi - drug effects; Superior Colliculi - metabolism; Superior Colliculi - pathology; Tyrosine kinase receptors; Up-Regulation - drug effects; Up-Regulation - physiology; Visual system; α-2-Adrenergic receptor agonist
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2006.09.005

The α-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 6 h 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, CNTFRα, 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.