Antiapoptotic effect of taurine against NMDA-induced retinal excitotoxicity in rats

作者：Lambuk, Lidawani; Iezhitsa, Igor^*; Agarwal, Renu; Bakar, Nor Salmah; Agarwal, Puneet; Ismail, Nafeeza Mohd

来源：NeuroToxicology, 2019, 70: 62-71.

DOI：10.1016/j.neuro.2018.10.009

• Glaucoma
• Retina
• Retinal ganglion cells (RGCs) apoptosis
• NMDA
• Excitotoxicity
• Brain-derived neurotrophic factor (BDNF)
• Taurine
• Neuroprotection

Objective: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure.
Methodology: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique.
Results: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 pm length (by 1.5-fold, p < 0.001) and per 100 mu m(2) area (by 1.41-fold, p < 0.05) of the GCL. After NMDA exposure, visible axonal swelling was observed in optic nerve sections. In comparison with the changes observed in the NMDA treated group, the TAU treated group showed fewer prominent changes; axonal swelling was less frequent and less marked. Additionally, no marked glial cell changes were observed in the TAU-pretreated group. All TAU treated groups, particularly the pre-treated group, showed a significant decrease in the NMDA-induced optic nerve damage, with a 50% reduction (p < 0.001) in the mean grading compared to NMDA group. For the same, there was 25% decrease in co- and post-treatment groups, as compared with the NMDA group. Pre-treatment with TAU abolished apoptotic response to NMDA as indicated by decrease in the number of TUNEL- and caspase-3-positive cells. TAU pretreatment also increased the Bcl-2 level (by 2.80-fold, p < 0.001) and decreased the level of Box (by 34%, p < 0.01), and activity of caspase-3 (by 36%, p < 0.001) compared to NMDA group.
In conclusion: our study revealed that pre-treatment with TAU prevents NMDA-induced retinal cell apoptosis more effectively than co- and post-treatment with TAU.

• 出版日期2019-1