Nn. Osborne et al., PROTECTION OF RABBIT RETINA FROM ISCHEMIC-INJURY BY FLUPIRTINE, Investigative ophthalmology & visual science, 37(2), 1996, pp. 274-280
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.