Dose-dependent and combined effects of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters.
This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine (L-NA) on the survival of retinal ganglion cells (RGCs) at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 (1.0, 3.0 and 4.5 mg/kg) and L-NA (1.5, 3.0, 4.5 and 6.0 mg/kg) increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.
Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China.
Yaoyu
Y
Li
Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
An'an
A
Yang
Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China.
Tingting
T
Zhu
Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Zhao
Z
Liu
Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Siwei
S
You
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Kwok-Fai
KF
So
N-methyl-D-aspartate receptor; hamster; neuronal survival; nitric oxide synthase; optic nerve transection; retinal ganglion cells