High glucose enhances oxidative stress-induced cell death in cultured neuronal cells

Retinal neurodegeneration occurs even before clinically detectable diabetic vascular retinopathy in diabetic patients. We have previously reported that a high-fat diet, which increases systemic oxidative stress, leads to retinal dysfunction in a mouse model of diabetes at an early stage. In this study, we investigated the effect of high glucose on oxidative stress-induced neuronal cell death in vitro. Neuro2a cells, a mouse neuronal cell line, were incubated with serum-free medium containing 25 - 100 mM glucose for 24 h, followed by caused oxidative stress with 200 - 400 μM sodium nitroprusside (SNP), a nitric oxide donor. Cell viability was determined by MTT assay. Pretreatment with glucose dose-dependently enhanced SNP-induced cell death. Treatment with glucose alone did not cause cell death in Neuro2a cells. The same concentrations of D-mannitol had no effect on the viability of the cells exposed to SNP, suggesting that the effect of glucose was not due to osmotic stress. These results indicate that high glucose enhances oxidative stress-induced neuronal cell death, suggesting that hyperglycemia may increase neuronal vulnerability and contribute to neurodegeneration in early diabetic retinopathy.