PURPOSE. α2-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. α2-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 deter- mined 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 α2-adrenergic antagonist, completely prevented the induction of ERK phosphorylation. Immunocytochemical studies showed that the increase in ERK phosphorylation occurred mainly in Muller cells. In the brain, xylazine injection resulted in a decrease in ERK phosphorylation CONCLUSIONS. Our results indicate that systemically administered α2- adrenergic agonists selectively activate ERKs in retinal Muller cells. The induced activation of ERKs in Muller cells is probably one of the early events that result in photoreceptor protection. These results also indicate that Muller cells are unique in response to α2-adrenergic agonists and imply a role for Muller cells in α-adrenergic agonist-induced photoreceptor protection.
|Original language||English (US)|
|Number of pages||6|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Dec 1 1998|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience