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C. e. Zangalli, D. S. Streit, A. M. Dantas, N. Calixto; The Effects of Brimonidine Tartrate on Retinal Spreading Depression. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5581.
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To investigate the influence of brimonidine tartrate (α2 agonist) on the propagation of retinal SD waves as it has been postulated to have protective effects on neuronal tissue.
We performed 14 experiments on fragments of retinal preparations of White Leghorn chicks from 3 to 8 days after hatching. Immediately after decapitation the eyeballs were removed and sectioned along the equator. Fragments of retina were transferred to a chamber and infused with Ringer solution (RS) driven by a peristaltic pump in order to maintain the RS flowing at a rate from 0.80 to 0.85 ml/min. The temperature in the chamber was set at 30°C by means of a thermostatic bath. RS composition in mM was: NaCl 100, KCl 6, CaCl2 2, MgSO4 1, NaHPO4 1, NaHCO3 30 and glucose 20. The presence or absence of SD was detected by recording its concomitant slow voltage variations through two pore electrodes connected to a Grass polygraph. All experiments started with a control procedure. Firstly, the retina infused with RS was mechanically stimulated by a sharpened tungsten wire, triggering a SD. Next, the infusion was changed to RS containing 0.1% brimonidine tartrate (0.1% RS/BT) and the retina was mechanically stimulated twice with an interval of 15 min. Afterwards, the infusion was returned to RS and 15 min later the retina was mechanically stimulated.
Our data demonstrated that brimonidine tartrate reduced the amplitude of the negative potential shift in 25.66% (from 20.46±2.64 mV to 15.21±2.70 mV) and decreased its duration in 47.79% (from 38.74±7.78 sec to 20.23±3.55 sec) in a reversible manner in all experiments (N=14).
When the brimonidine tartrate binds to an α2 adrenergic receptor, this receptor activates a G protein that inactivates the enzyme adenylate ciclase. This reduces the intracelular cAMP levels and the protein Kinase A (PKA) resulting in an inactivation of the Ca++ channels and in the closure of the K+ channels at the same time. This is one of the possible explanations for the effect of brimonidine tartrate over the SD as well as its possible neuroprotector effect.,
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