The effects of pre-
or post-treatment with the a2 agonist Brimonidine (BMD), on retinal
ganglion cell (RGC) survival after ischemia was investigated in adult Sprague-Dawley
rats. RGCs were labeled with Fluorogold (FG) applied to both superior colliculi
and 7 days later, the left opthalmic vessels were ligated for 90 minutes. In
one group of rats, 1 hour before ischemia, BMD was given systemically (one i.p.
injection of saline, or saline containing 0.1 or 1 mg/kg b.w. of BMD), or
topically (two 5 ml drops of saline alone, or saline
containing 0.5% or 0.1% of BMD). In another group of rats, 1 hour after
ischemia BMD (1 mg/kg) was administered i.p. Rats were processed 7, 14 or 21 days later, and RGC
survival was estimated by counting FG-labelled cells in 12 standard areas of
each retina. In the pre-treated group of rats, 7 d after ischemia, mean RGC densities
decreased to 53%, 91% and 91% of their contralateral values, for
vehicle, 1 and 0.1 mg/kg of BMD, respectively, for the systemically treated groups, and to 54%, 96% and 99% of
their contralateral values, for vehicle, 0,1% and 0,5% of BMD, respectively, for the topically treated groups. For the post-treated group of rats, 7 d after ischemia mean
RGC densities decreased to 53% and 72% of their contralateral values for
vehicle and BMD, respectivley, and at 21 d mean
RGC densities were 38% and 60% for the vehicle and BDM, respectively.
Thus, BMD has a strong
neuroprotective effect on ischemia induced-RGC death when administered i.p. or
topically prior to insult.
Support: FIS 98/0341-99/1090,
and an Allergan unrestricted grant.