PROTECTION OF RABBIT RETINA FROM ISCHEMIC-INJURY BY FLUPIRTINE

Purpose. The aim of this study was to determine whether flupirtine can slow down the changes seen in the rabbit retina after ischemia-reperf usion. Methods. A suction-cup procedure, which raises intraocular pres sure, was used to give an ischemic insult to the rabbit retina. Electr oretinograms were recorded before ischemia and at different periods af ter ischemia. In some instances, flupirtine was injected into the eye before ischemia. Immunohistochemistry was used to study the effect of ischemia-reperfusion on the gamma-aminobutyric acid (GABA) immunoreact ivity and uptake of serotonin by the retina. The effect of flupirtine and ischemia on retinal adenosine triphosphate (ATP) levels were deter mined in in vivo and in vitro experiments. Results. Ischemia for 75 mi nutes causes a change in the nature of normal GABA immunoreactivity an d a reduction in the b-wave of the electroretinogram. When flupirtine is injected into the vitreous humor at the onset of ischemic insult, t he changes in GABA immunoreactivity are reduced and the recovery of th e reduced b-wave of the electroretinogram after defined reperfusion ti mes is enhanced significantly. Rat retinas incubated in vitro in physi ological solution containing flupirtine caused a significant rise in t he tissues' ATP content compared with control samples. However, incuba tion of the tissue in physiological solution saturated with nitrogen c aused a drop in retinal ATP levels. Addition of flupirtine prevented t his decrease from taking place. Serotonin injected into the vitreous h umor of the rabbit eye is taken up by certain amacrine cells. The amou nt of serotonin taken up is reduced greatly in retinas, as judged by i mmunohistochemistry when tissues are subjected to ischemia. Because th e ischemia was shown to cause a drop in the tissue ATP level, it is co ncluded that this is the cause of the reduced uptake of exogenous sero tonin. Injection of flupirtine into the vitreous humor during ischemia enhanced the uptake of serotonin. Conclusions. Combined data show tha t flupirtine is a neuroprotective agent in retinal ischemia and that o ne mode of its mechanism of action is to influence ATP levels. Flupirt ine may lower the activity of NMDA receptors, thus causing ATP levels to be less affected in the presence of the drug as a secondary effect.