Alpha2-adrenergic agonists selectively activate extracellular signal-regulated kinases in Müller cells in vivo.
OBJECTIVE
Alpha2-adrenergic agonists have specific and selective effects on the retina to induce expression of basic fibroblast growth factor and to protect photoreceptors. This work explores the signaling pathway that mediates these effects.


METHODS
Alpha2-adrenergic agonists xylazine and clonidine were administered systemically to male adult Sprague-Dawley rats. The activation state of extracellular signal-regulated kinases (ERKs) in the retina was assessed by immunoblot analysis, using antibodies that specifically recognize the dually phosphorylated forms of p44/p42 ERKs. Localization of phosphorylated ERKs was determined by immunocytochemistry.


RESULTS
Intramuscular injection of 6 mg/kg xylazine induced an increase in ERK phosphorylation in the retina within 30 minutes that lasted 3 hours. Xylazine induced ERK phosphorylation at 1 mg/kg and reached a maximum at 10 mg/kg. Injection of clonidine also induced ERK phosphorylation in the retina. Yohimbine, a specific alpha2-adrenergic antagonist, completely prevented the induction of ERK phosphorylation. Immunocytochemical studies showed that the increase in ERK phosphorylation occurred mainly in Müller cells. In the brain, xylazine injection resulted in a decrease in ERK phosphorylation.


CONCLUSIONS
Our results indicate that systemically administered alpha2-adrenergic agonists selectively activate ERKs in retinal Müller cells. The induced activation of ERKs in Müller cells is probably one of the early events that result in photoreceptor protection. These results also indicate that Müller cells are unique in response to alpha2-adrenergic agonists and imply a role for Müller cells in alpha2-adrenergic agonist-induced photoreceptor protection.
Department of Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
M
M
Peng
Y
Y
Li
Z
Z
Luo
C
C
Liu
A M
AM
Laties
R
R
Wen
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D014991:Xylazine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D014991:Xylazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D003000:Clonidine