Optic Nerve Degeneration and Reduced Contrast Sensitivity Due to Folic Acid Deficiency: A Behavioral and Electrophysiological Study in Rhesus Monkeys

Abstract

Citation: Santandrea E, Sani I, Morbioli G, Multari D, Marchini G, Chelazzi L. Optic nerve degeneration and reduced contrast sensitivity due to folic acid deficiency: a behavioral and electrophysiological study in rhesus monkeys. 2018;59:6045-6056. https://doi.org/10.1167/iovs. PURPOSE. The purpose of the research was to elucidate the role of folic acid (B 9 ) deficiency in the development of nutritional optic neuritis and to characterize the neurophysiological consequences of optic nerve degeneration in the cortical visual system. METHODS.A combined behavioral and electrophysiological approach was applied to study luminance contrast sensitivity in two macaque monkeys affected by nutritional optic neuritis and in two healthy monkeys for comparison. For one monkey, a follow-up approach was applied to compare visual performance before onset of optic neuropathy, during the disease, and after treatment. RESULTS. Optic nerve degeneration developed as a consequence of insufficient dietary intake of folic acid in two exemplars of macaque monkeys. The degeneration resulted in markedly reduced luminance contrast sensitivity as assessed behaviorally. In one monkey, we also measured visual activity in response to varying contrast at the level of single neurons in the cortical visual system and found a striking reduction in contrast sensitivity, as well as a marked increase in the latency of neuronal responses. Prolonged daily folate supplementation resulted in a significant recovery of function.CONCLUSIONS. Folic acid deficiency per se can lead to the development of optic nerve degeneration in otherwise healthy adult animals. The optic nerve degeneration strongly affects contrast sensitivity and leads to a distinct reduction in the strength and velocity of the incoming signal to cortical visual areas of the macaque brain, without directly affecting excitability and functional properties of cortical neurons.