The neuroprotective
effects of systemic or topical administration of unoprostone isopropyl (U.I.)
on retinal ganglion cell (RGC) survival after transient ischemia were studied
in adult Sprague-Dawley rats. RGCs were labeled with Fluorogold (FG) applied to
both superior colliculi. Seven days later, the left eyes were given 60 minutes
of ischemia by ligature of the ophthalmic vessels. One group of rats received within 30 minutes after the ischemic insult, one
single i.p. injection of vehicle
or 0,1, 1 or 10 mg/kg of U.I.; these rats were analized 5, 7 or 9 days later. A second group received two daily drops of Rescula® (0,15% U.I.) or saline;
these rats were analized 5, 14
or 21 days later. Animals were perfused, both retinas prepared as whole-mounts
and examined under fluorescent microscopy. In rats treated systemically with
vehicle, mean densities of labelled RGCs
decreased to 68%, 68 and 67% of contralateral values at 5, 7 and 9 days, respectively.
Treatment with 0,1, 1 or 10 mg/kg of U.I. resulted in significanly greater
densities at 5 days, but not at 7 or 9 days. In the rats treated topically,
mean densities of labelled RGCs decreased to 75%, 65% or 64% of contralateral
values at 5, 14 or 21 days, respectively,
Topical administration of U.I. resulted in significanly greater
densities at 5 but not at 14 or 21 days. Thus, U.I. administered systemically
or topically has a significant neuroprotective effect 5 days after ischemia.
Supported by FIS
98/0341 and a Ciba Vision unrestricted grant.