Abstract
Purpose: :
To investigate the effect of thalidomide in N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity.
Methods: :
Eight-week-old male Wistar rats were received oral intake of thalidomide every day throughout the experiments. Intravitreal injection of NMDA was performed 24 hrs after first oral intake. The eyes were enucleated 1 and 7 days after intravitreal injection. The level of tumor necrosis factor-α (TNF-α) in the retina was examined by ELISA. Nuclear factor-ΚB (NF-B) p65 protein levels were estimated by Western blot. The effect of thalidomide on NMDA-induced nerurotoxicity was evaluated by morphometry of cells in the retinal ganglion cell layer (RGCL) with cresyl violet staining.
Results: :
The level of TNF-α in the retina was significantly increased 24 hrs after NMDA injection. As shown previously, the level of NF-B p65 protein was increased in the retina 24 hrs after NMDA injection. Systemic administration of thalidomide suppressed both elevation of TNF-α and NF-B p65 protein induced by NMDA. Morphometry of flatmounted retina demonstrated that thalidomide significantly ameliorated the cell death in the RGCL induced by NMDA.
Conclusions: :
The neuroprotective effect of thalidomide may be related to its inhibitory effects of TNF-α production and sequential upregulation of NF-B p65.
Keywords: excitatory amino acid receptors • retina: neurochemistry • drug toxicity/drug effects