The evaluation of retinal protection of ß–blockers against glutamate–induced neurotoxicity in isolated rat retina.

Abstract

Abstract: : Purpose: Several ß–blockers are reported to possess an optic nerve head flow increasing effect as well as an intraocular pressure (IOP) lowering effect. In this study, we examined the neuroprotective effect of ß–blockers against excitotoxicity induced by glutamate in isolated rat retinas. Since glutamate receptors have two ion channel types, this study also attempted to find which type of glutamate receptor is involved in the protective effect. To investigate retinal damage, we evaluated the amount of LDH (lactate dehydrogenase) released in the medium. Methods: Retinas were isolated from 8 week–old male Spraque–Dawley rats and, after treating them for 1 hour with 10 mM glutamate, they were incubated in aCSF (artificial cerebrospinal fluid) and the LDH released in the medium was measured every hour. One of the ß–blockers (timolol maleate, betaxolol hydrochloride, and carteolol hydrochloride) was administrated to medium at the dose of 100 µM during glutamate exposure and in glutamate–free medium after glutamate exposure. In the same way, we added N–methyl–D–aspartate (NMDA) type receptor antagonist MK–801 and added non–NMDA type receptor antagonist DNQX (6,7–dinitroquinoxaline–2,3–dione) so that the final concentration is 30 µM and 100 µM, respectively. Results: LDH release from rat retinas treated with carteolol hydrochloride was significantly lower compared to that of the control. Furthermore, the released LDH was significantly suppressed by the DNQX addition to the control but a significant difference was not shown by the MK–801 addition. Conclusions: In this experimental model, the non–NMDA type glutamate receptor was involved in glutamate–mediated retinal toxicity. Carteolol hydrochloride might have a protective effect by suppressing the damage caused by this receptor.

Keywords: retinal culture • neuroprotection • excitatory amino acid receptors