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Rojas and Gonzalez-Lima Dovepress and recent research supports its potential benefits in retinal disease, stroke, neurodegeneration, neuromuscular disorders, and memory and mood disorders. This therapeutic revolution is being favored by progress in the field of photobiology, aided by a twenty-first century reemergence of interest in bioenergetics. Current progress in photochemistry, genetics, informatics, and neuroimaging has allowed quantifying and differentiating the effects of light and other forms of electromagnetic radiation on biological tissues at different levels of analysis. Throughout its development in the last 40 years, the concept of using “light to heal” has had an esoteric and suspicious connotation to the western contemporary bio- medical mind. As illustrated by a reviewer’s comments from a reputable biomedical journal to a recent manuscript on LLLT, the “curious effects” of light therapy have had the misfortune of being classified as a laughable school of thought in the tradition of astrology and Mesmer’s ani- mal magnetism. We are constantly exposed to light with apparently innocuous or trivial biological effects. Even when biological effects of light can be demonstrated, these are highly variable, present nontraditional dose-response curves, or lack a mechanistic explanation within traditional pharmacodynamic paradigms. A recent review stated that “widespread uncertainty and confusion exists about the mechanisms of action of LLLT at the molecular, cellular, and tissue levels.”1 Thus, it is not surprising that LLLT lacks scientific appeal and has been denied entrance into mainstream medicine. Even when the benefit of doubt is allowed, LLLT could easily be regarded as a science-fiction construct or wishful thinking. Yet, compelling data on the potential clinical value of LLLT is available. A sound theory on the mechanism of action of LLLT implicating regulation of mitochondrial function has been advanced, and available data support that light-tissue interactions have special implications in highly metabolically-active excitable tissues, including the retina and the brain. Although there is still a lot to learn about mechanistic light-tissue interac- tions in the nervous system and the retina, evidence shows that LLLT can enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. This review will briefly describe the cur- rent proposed photochemical mechanisms underlying the neurobiological effects of LLLT. A summary of current knowledge about LLLT dosimetry relevant for its variable effects in the nervous system, including noninvasive in vivo transcranial effects is also presented. A summary of key in vitro, preclinical, and clinical studies supporting the protective and enhancing effects of LLLT in a number of pathogenic conditions including cytotoxicity, mitochon- drial dysfunction, and hypoxia/ischemia in the retina and the central nervous system is presented. The data on LLLT suggest it can exert effective, reproducible, and meaningful changes in the normal and dysfunctional nervous tissue. This highlights the value of LLLT as a novel and useful 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. What is LLLT? Light is a type of electromagnetic radiation with both wave-like and particle-like properties. Living organisms are immersed in a vast ocean of electromagnetic radiation, which consists of periodic oscillations in electromagnetic fields that travel space and are thus able to transfer energy. Hence, light is a form of energy called luminous energy. A wave of electromagnetic radiation has a unidirectional vector and can be characterized in terms of its wavelength (λ = the distance between successive peaks or troughs), frequency (the number of oscillations per second), and amplitude (the difference between trough and peak). A complex mixture of waves with different frequencies, amplitudes, and wavelengths are absorbed, scattered, and reflected by objects, including biological material. Light of only one wavelength is called monochromatic. In modern quantum physics, electromagnetic radiation consists of photons, which are particles (quanta) of energy that travel at a speed of 3 × 108 m/second. The brightness of light is the number of photons and the color of the light is the energy contained in each photon. LLLT can be defined as the use of directional low-power and high-fluence monochromatic or quasimonochromatic light from lasers or light-emitting diodes (LEDs) in the red to near-infrared wavelengths (λ = 600–1100 nm) to modulate a biological function or induce a therapeutic effect in a nondestructive and nonther- mal manner.2,3 The effects of LLLT implicate conversion of luminous energy to metabolic energy with a subsequent modulation of the biological functioning of cells. Thus, LLLT is commonly known as photobiomodulation. It could also be called photoneuromodulation when nerve cells are the target. LLLT differs from the conventional effects of high-energy photon delivery commonly associated with lasers, which are mediated by a greater release of energy and result in heating and tissue destruction through dissec- tion, ablation, coagulation, and vaporization. Compared to Eye and Brain 2011:3 50 submit your manuscript | www.dovepress.com DovepressPDF Image | Low-level light therapy of the eye and brain
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