TY - JOUR
T1 - In vitro and in vivo protective effects of eliprodil in the retina
AU - Chandler, M. L.
AU - Pang, I. H.
AU - Doshi, R.
AU - Wexler, E. M.
AU - Walters, R. J.
AU - Nawy, S.
AU - Desantis, L.
AU - Kapin, M. A.
PY - 1997
Y1 - 1997
N2 - Purpose. Evaluate the protection of eliprodil, an NMDA-receptor polyamine-site antagonist, against excitatory amino acid- or ischemia-induced insults on retinal cells and retina in vivo. Methods, Neonatal rat retinal ganglion cells (RGC) were used in whole-cell recording and survival (assayed by counting Di-I-labelled cells) studies. In in vivo experiments, retinal ischemia, as assessed by a cessation of ERG activity, was effected in rabbits by raising intraocular pressure. Excitotoxicity was produced by intravitreal injection of NMDA (20 nmol in 5 /xl), which caused a decrease of cells in the ganglion cell layer (GCL) and retinal choline acetyltransferase activity (ChAT). Results. Eliprodil dose-dependently suppressed NMDA (200 /iM)-activated currents in RGC, and prevented cell death induced by 100 /*M glutamate with an ECSO of 1 nM. At 100 nM of eliprodil, 100% of cells survived the glutamate insult; however, eliprodil did not prevent anoxia-induced in vitro RGC cell death. In the anesthetized rabbit, retinal ischemia resulted in a 60-70% depression in ERG a- and b-waves. Eliprodil (1-10 mg/kg, i.p.) administered prior to ischemia, in a dose-dependent manner, attenuated the depressed ERG throughout a 48 h period. At. 10 mg/kg, i.p., eliprodil also completely prevented the loss of retinal ChAT and loss of cells in the GCL. Conclusions. Eliprodil is protective against cytotoxic insults due to ischemia or excitatory amino acids in retinal tissues and cells.
AB - Purpose. Evaluate the protection of eliprodil, an NMDA-receptor polyamine-site antagonist, against excitatory amino acid- or ischemia-induced insults on retinal cells and retina in vivo. Methods, Neonatal rat retinal ganglion cells (RGC) were used in whole-cell recording and survival (assayed by counting Di-I-labelled cells) studies. In in vivo experiments, retinal ischemia, as assessed by a cessation of ERG activity, was effected in rabbits by raising intraocular pressure. Excitotoxicity was produced by intravitreal injection of NMDA (20 nmol in 5 /xl), which caused a decrease of cells in the ganglion cell layer (GCL) and retinal choline acetyltransferase activity (ChAT). Results. Eliprodil dose-dependently suppressed NMDA (200 /iM)-activated currents in RGC, and prevented cell death induced by 100 /*M glutamate with an ECSO of 1 nM. At 100 nM of eliprodil, 100% of cells survived the glutamate insult; however, eliprodil did not prevent anoxia-induced in vitro RGC cell death. In the anesthetized rabbit, retinal ischemia resulted in a 60-70% depression in ERG a- and b-waves. Eliprodil (1-10 mg/kg, i.p.) administered prior to ischemia, in a dose-dependent manner, attenuated the depressed ERG throughout a 48 h period. At. 10 mg/kg, i.p., eliprodil also completely prevented the loss of retinal ChAT and loss of cells in the GCL. Conclusions. Eliprodil is protective against cytotoxic insults due to ischemia or excitatory amino acids in retinal tissues and cells.
UR - http://www.scopus.com/inward/record.url?scp=0345228442&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0345228442&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0345228442
SN - 0146-0404
VL - 38
SP - S147
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 4
ER -