Julio C Rojas1,2, F Gonzalez-Lima1
1Departments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX; 2Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA
Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain.
LLLT or photobiomodulation refers to the use of low-power and high-fluence light from lasers or LEDs in the red to near-infrared wavelengths to modulate a biological function. Cytochrome oxidase is the primary photoacceptor of LLLT with beneficial eye and brain effects since this mitochondrial enzyme is crucial for oxidative energy metabolism, and neurons depend on cytochrome oxidase to produce their metabolic energy. Photon-induced redox mechanisms in cytochrome oxidase cause other primary and secondary hormetic responses in neurons that may be beneficial for neurotherapeutic purposes. Beneficial in vivo effects of LLLT on the eye have been found in optic nerve trauma, methanol intoxication, optic neuropathy, retinal injury, retinitis pigmentosa, phototoxicity, and age-related macular degeneration. Beneficial in vivo transcranial effects of LLLT on the brain have been observed in anoxic brain injury, atherothrombotic stroke, embolic stroke, ischemic stroke, acute traumatic brain injury, chronic traumatic brain injury, neurodegeneration, age-related memory loss, and cognitive and mood disorders. No adverse side effects have been reported in these beneficial applications of LLLT in animals and humans. The authors conclude that LLLT is a safe and beneficial approach, based on scientifically sound mechanisms of action of red to near-infrared light on cytochrome oxidase, with neurotherapeutic promise for a wide range of ophthalmological, neurological, and psychological conditions.