Lactate: More Than Merely a Metabolic Waste Product in the Inner Retina

The retina is an extension of the central nervous system and has been considered to be a simplified, more tractable and accessible version of the brain for a variety of neuroscience investigations. The optic nerve displays changes in response to underlying neurodegenerative diseases, such as stroke, multiple sclerosis, and Alzheimer's disease, as well as inner retinal neurodegenerative disease, e.g., glaucoma. Neurodegeneration has increasingly been linked to dysfunctional energy metabolism or conditions in which the energy supply does not meet the demand. Likewise, increasing lactate levels have been correlated with conditions consisting of unbalanced energy supply and demand, such as ischemia-associated diseases or excessive exercise. Lactate has thus been acknowledged as a metabolic waste product in organs with high energy metabolism. However, in the past decade, numerous beneficial roles of lactate have been revealed in the central nervous system. In this context, lactate has been identified as a valuable energy substrate, protecting against glutamate excitotoxicity and ischemia, as well as having signaling properties which regulate cellular functions. The present review aims to summarize and discuss protective roles of lactate in various model systems (in vitro, ex vivo, and in vivo) reflecting the inner retina focusing on lactate metabolism and signaling in inner retinal homeostasis and disease.