Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye

There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid (KYNA) production in the neuroprotective effects of the ketogenic diet (KD). KD and ketone bodies (KBs) that are elevated during exposure to the KD each have a neuroprotective effect on retinal ganglion cells in a rat model of N-methyl-D-aspartate (NMDA)-induced neuronal damage. Chronic exposure to KD also increases KYNA concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of KYNA in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three KBs overproduced during KD. Whether KD-induced enhancement of KYNA production would translate into a clinically significant improvement in certain eye diseases like glaucoma and retinal neurodegenerations awaits further experimental and clinical verification. Here, we review evidence implicating KYNA in the efficacy of KD in eye diseases associated with neurodegeneration.