A Ketogenic Diet May Offer Neuroprotection in Glaucoma and Mitochondrial Diseases of the Optic Nerve

Abstract

Glaucoma is a chronic optic nerve disease in which the primary damage occurs to the retinal ganglion cell axons. Therapies that prevent the death of retinal ganglion cells should be theoretically beneficial. Despite promising preclinical studies, however, almost all clinical studies with pharmacological approaches for neuroprotection in neurologic and eye diseases, including glaucoma, have so far failed to show efficacy. As the evidence supporting the neuroprotective efficacy of a ketogenic diet (KD) in a number of neurodegenerative diseases continues to grow, it is conceivable that this metabolic approach might be useful in chronic glaucoma. Putative cellular mechanisms underlying the neuroprotective activity of the KD have been identified in neurological studies, including effects on energy metabolism, the GABA system, glutamate-mediated toxicity, antioxidant mechanisms, programmed cell death, anti-inflammatory mechanisms, and the production of kynurenic acid. Of note, the same mechanisms are thought to be involved in glaucoma. Given these mechanistic similarities, testing the KD for its efficacy in neurodegenerative diseases of the eye is proposed.