Abstract
Purpose: :
Brimonidine is an α2-adrenergic receptor agonist that is known to be neuroprotective for ganglion cells in injured rat retina. This effect may involve Müller cells. Among other functions, Müller cells stabilize and contribute to homeostasis in the retina. The purpose was to study the effects of transient retinal ischemia on Müller cells after pre-treatment with brimonidine or vehicle.
Methods: :
Ninety minutes of retinal ischemia was induced by unilateral ligature of the left ophthalmic vessels in adult Sprague Dawley rats. Prior to surgery, animals were treated topically with two 5 µl drops of 0.5 % brimonidine or vehicle (0.9 % NaCl). Left retinas were collected between 6 hours and 14 days after injury and analyzed for mRNA using qRT-PCR. Whole eyes were collected 12 hours or 3 days after injury for immunohistochemical analysis. Müller cell markers vimentin and glutamine synthetase (GS), astrocyte marker GFAP and neural stem cell marker nestin were analyzed. Results were compared to levels and expression patterns in normal retinas.
Results: :
The expression of vimentin was transiently increased while GS was transiently decreased after injury. GFAP expression increased and the levels remained above normal 2 weeks after injury. GFAP localized to both astrocytes in the ganglion cell layer and Müller cells. There was no difference between brimonidine- and vehicle-treated retinas when analyzing vimentin, GS and GFAP. The neural stem cell marker nestin was localized to Müller cells and increased substantially after injury from very low levels. This increase was reduced by brimonidine treatment.
Conclusions: :
The altered levels of vimentin, GS and GFAP were not differing between retinas treated with brimonidine or vehicle, which shows that brimonidine treatment does not affect these glial cell markers. The altered expression of vimentin in Müller cells may reflect an ischemia specific response that appears to differ from other injuries. The restrained increase in nestin expression that was evoked by injury, indicated that brimonidine suppresses this stem cell like feature in Müller cells. In summary, our results suggest that brimonidine may have a specific effect on Müller cells.
Keywords: Muller cells • ischemia • neuroprotection