We have previously reported that β(3)-adrenoceptor agonists dilate retinal blood vessels, but their effects on retinal neurons have been unclear. In this study, we examined the action of the β(3)-adrenoceptor agonist
CL316243 against
retinal damage induced by
intravitreal injection of
N-methyl-D-aspartate (
NMDA) in rats.
CL316243 was injected into the vitreous cavity before, with, or after intravitreal
NMDA injection. Seven days after
NMDA injection, cell loss in the
ganglion cell layer (GCL) and thinning of the inner plexiform layer were observed. The reduction in the number of cells in the GCL was diminished by injection of
CL316243 at 15, 30, 60, or 120 min after
NMDA injection, whereas no significant protective effect was observed when
CL316243 was administered 240 min after
NMDA injection. Neither preinjection of
CL316243 30 min before
NMDA nor simultaneous injection of
CL316243 with
NMDA exerted any protective effect. The β(3)-adrenoceptor antagonist L748337 almost completely abolished the protection conferred by
CL316243 injection 120 min after
NMDA injection. The number of
parvalbumin-positive amacrine cells was decreased in eyes examined 1 day after
NMDA treatment, but this was prevented by
CL316243 injection at 120 min after
NMDA injection. These results suggest that
CL316243 exerts protective effects against
NMDA-induced damage by stimulation of β(3)-adrenoceptors. β(3)-adrenoceptor agonists may be effective candidates for the treatment of
retinal diseases associated with
glutamate-induced excitotoxicity, including
glaucoma and
diabetic retinopathy.