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Renata Fleming, Vinicius Oliveira, Gabriela Alencar, Nassim Calixto, Sebastiao Cronemberger, Patricia Gardino, Adalmir Dantas; THE EFFECTS OF BRIMONIDINE ON RETINAL SPREADING DEPRESSION. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6355. doi: https://doi.org/.
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Brimonidine is a drug used in the management of glaucoma and is the most modern alpha(2) - adrenergic receptor agonist available. α2 - adrenergic receptor agonists have been shown to be neuroprotective in various experimental models, but the molecular and cellular targets leading to these actions are still poorly defined. Brimonidine, a drug used in the management of glaucoma throughout the world, is the most modern alpha2 - adrenergic receptor agonist available. α2 - adrenergic receptor agonists have been shown to be neuroprotective in various experimental models. However, the molecular and cellular targets leading to these actions are still poorly defined. The spreading depression (SD) of electric activity of the retina was initially described by Gouras. SD is a wave of cellular depolarization and has been related to many central nervous diseases. The aim of this study is to investigate the role of brimonidine tartarate (BT) on retinal SD using the chicken retina as a model.
Initially we identified the α2 - adrenergic receptor in the retinal chicken tissue using immunoblotting and immunohistochemistry. We then applied electrophysiological methods to investigate the effects of BT over the retinal spread depression in the chicken retina. The slow voltage variation was measured by two electrodes connected to a Grass polygraph while the retina was superfused for 15 minutes with a modified Ringer solution (RS) added to concentrations of BT: 0, 100, 300, 1000, 2200 and 4000 mM. Afterwards, the retina was superfused with RS, twice. We also measured the time interval of the SD passage through the electrodes in order to obtain its velocity.
Western blotting showed the presence of an α2a- adrenergic receptor in the retinal tissue. Immunohistochemistry demonstrated that α2a - adrenergic receptors are present in Müller cells (Figure 1). The electrophysiological studies demonstrated a significant decrease of the voltage shift at 4000mM (P<0.01) and with the RS immediately after 4000mM (P<0.001), but not with the second RS. The time of SD passage through the electrodes was significantly longer at 2200 mM (P<0.05) and at 4000mM (P<0.001), and with the RS immediately after 4000mM P<0.001, but not with the second RS.
Our data suggest that BT neuroprotective actions might be mediated by Müller cells and their connections present in different layers of the chicken retina.
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