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R. S. Duncan, H. Xin, P. Koulen; Neuroprotection of Mouse Retina Ganglion Cells by N-Acylethanolamines. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3694.
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N-Acylethanolamines (NAEs) are lipids upregulated in response to cell and tissue injury and some have been shown to be involved in neuroprotection. Arachidonylethanolamide is a well characterized NAE that is an endogenous ligand at cannabinoid and vanilloid receptors. The function and molecular target of other NAEs that do not bind to these receptors, such as NAE 18:2, are unclear and have thus prompted us to measure their neuroprotective properties in the retina. We hypothesized that NAE 18:2 protects retinal ganglion cells from glutamate excitotoxicity.
Whole retinas were isolated from C57BL/6 mice and maintained as organotypic cultures. Retinas were treated with NAE 18:2 over a range of physiologically relevant concentrations for 6 hours followed by addition of an excitotoxic insult with 100µM glutamate for 16 - 20 hours. Loss of neuronal viability and cell death were assessed using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) histochemistry, cell specific immunohistochemistry and fluorescence microscopy.
Exposure of retinas to 100µM glutamate resulted in a dramatic increase in retinal ganglion cell (RGCs) death. Preincubation of retinas with NAE 18:2 prior to glutamate exposure resulted in a dose-dependent decrease in the number dead or dying RGCs with high physiological concentrations reducing the number of dead or dying RGCs to to that of the Glutamate vehicle control group.
The highly significant, dose-dependent reduction of glutamate-induced RGC death by treatment with NAE 18:2 reveals a neuroprotective function for NAEs that do not bind to cannabinoid and vanilloid receptors. These results provide a rationale for the use of NAEs as potential therapeutic compounds in acute and chronic neurodegenerative diseases of the retina.
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