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

Lönngren, Ulrika; Näpänkangas, Ulla; Lafuente, Maria; Mayor, Sergio; Lindqvist, Niclas LU ; Vidal-Sanz, Manuel and Hallböök, Finn (2006) In Brain Research Bulletin 71(1-3). p.208-218
Abstract

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... (More)

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, p75NTR, 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, p75NTR, 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 p75NTR. 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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
α-2-Adrenergic receptor agonist, Injury, Neurotrophic factor, Real time PCR, Tyrosine kinase receptors, Visual system
in
Brain Research Bulletin
volume
71
issue
1-3
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:33750993499
ISSN
0361-9230
DOI
10.1016/j.brainresbull.2006.09.005
language
English
LU publication?
no
id
719da3dc-cef4-4044-800b-884656763ad0
date added to LUP
2017-06-02 15:17:19
date last changed
2019-02-20 10:38:38
@article{719da3dc-cef4-4044-800b-884656763ad0,
  abstract     = {<p>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<sup>NTR</sup>, 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<sup>NTR</sup>, 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<sup>NTR</sup>. 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.</p>},
  author       = {Lönngren, Ulrika and Näpänkangas, Ulla and Lafuente, Maria and Mayor, Sergio and Lindqvist, Niclas and Vidal-Sanz, Manuel and Hallböök, Finn},
  issn         = {0361-9230},
  keyword      = {α-2-Adrenergic receptor agonist,Injury,Neurotrophic factor,Real time PCR,Tyrosine kinase receptors,Visual system},
  language     = {eng},
  month        = {12},
  number       = {1-3},
  pages        = {208--218},
  publisher    = {Elsevier},
  series       = {Brain Research Bulletin},
  title        = {The growth factor response in ischemic rat retina and superior colliculus after brimonidine pre-treatment},
  url          = {http://dx.doi.org/10.1016/j.brainresbull.2006.09.005},
  volume       = {71},
  year         = {2006},
}