Neuronal cell signaling plays a key role in retinal ganglion cell (RGC) generation. We identified key signaling molecular events in RGCs that promote glutamate excitotoxicity. Docosahexaenoic acid (DHA, 22:6n-3) is a polyunsaturated fatty acid that is essential for normal signal transduction functions. DHA is selectively taken up by photoreceptors and synapses, including those on RGCs, and actively incorporated into membrane phospholipids. DHA is transported apically to photoreceptor outer segments and basally to synaptic terminals and is involved in the pathophysiology of neurodegeneration. DHA may be involved in survival and endogenous neuroprotection in ganglionar cell synapses. We conducted an autoradiographic study using H3-DHA of human and other retinas, demonstrating the enrichment of DHA in photoreceptors. We extended this study to the neural retina, demonstrating the enrichment of H3-labeled DHA in RGC photoreceptors. DHA prevents cell degeneration and apoptotic cell death in photoreceptor cells cultures and supports photoreceptor differentiation and growth. Activation of phospholipase A2 signaling pathways leads to the release of DHA, and its subsequent oxygenation to docosanoid metabolites. Docosanoids may be unique mediators of physiological processes in the retina.
Conclusion: While additional research is needed, docosanoids offer promise to understand aspects of glaucoma pathophysiology. The mechanism of action of a synthetic docosanoid, unoprostone isopropyl, may include upregulating signaling pathways essential for RGC survival.