Low-level light therapy of the eye and brain

Abstract

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.

Augmentation of cognitive brain functions with transcranial lasers

“…Thus, we estimated that about 1.2 J/cm 2 of the 60 J/cm 2 LLLT dose applied reached the surface of the prefrontal cortex. This value is similar to 1 J/cm 2 , the peak effective LLLT dose in neuron cultures for increasing cytochrome oxidase activity (Rojas and Gonzalez-Lima, 2011). …”

“…But for the field of low-level light/laser therapy (LLLT), development of a model of how luminous energy from red-to-near-infrared wavelengths modulates bioenergetics began with in vitro and in vivo discoveries in the last 40 years. Previous LLLT reviews have provided extensive background about historical developments, principles and applications (Rojas and Gonzalez-Lima, 2011, 2013; Chung et al, 2012). The purpose of this paper is to provide an update on LLLT's neurochemical mechanisms supporting transcranial laser stimulation for cognitive-enhancing applications.…”

Photobiomodulation improves the frontal cognitive function of older adults

“…34 Cerebral blood flow is increased due to the vasodilation that occurs after the release of nitric oxide. 37,39,40 Other studies using various mouse models showed that PBM effectively provided neuroprotection, 41,42 improved memory function, 43 and reduced brain tissue loss. [36][37][38] This mechanism is supported by previously reported animal experiments, which identified increases in cytochrome c oxidase and metabolic capacity following PBM.…”

Optical monitoring of retinal respiration in real time: 670 nm light increases the redox state of mitochondria

“…Cytochrome c oxidase (COX) in complex IV of the mitochondrial respiration chain has key points of deep red and infrared light absorbance, which can change the redox state of the copper heme in COX (Karu, 2008, Mason et al., 2014, Gonzalez-Lima and Rojas, 2011). Recently, absorbance of one of these wavelengths, 670 nm light, in the retina of aged animals has been shown to improve mitochondrial respiration, increasing their membrane potentials and improve ATP production (Kokkinopoulos et al., 2013, Gkotsi et al., 2014, Calaza et al., 2015).…”