Abstract
.Significance: Photobiomodulation (PBM) refers to the beneficial effects of low-energy light absorption. Although there is a large body of literature describing downstream physiological benefits of PBM, there is a limited understanding of the molecular mechanisms underlying these effects. At present, the most popular hypothesis is that light absorption induces release of nitric oxide (NO) from the active site of cytochrome oxidase (COX), allowing it to bind instead. This is believed to increase mitochondrial respiration, and result in greater overall health of the cell due to increased adenosine triphosphate production.Aim: Although NO itself is a powerful signaling molecule involved in a host of biological responses, less attention has been devoted to NO mechanisms in the context of PBM. The purpose of our work is to investigate wavelength-specific effects on intracellular NO release in living cells.Approach: We have conducted in-depth dosimetry analyses of NO production and function in an in vitro retinal model in response to low-energy exposure to one or more wavelengths of laser light.Results: We found statistically significant wavelength-dependent elevations (10% to 30%) in intracellular NO levels following laser exposures at 447, 532, 635, or 808 nm. Sequential or simultaneous exposures to light at two different wavelengths enhanced the NO modulation up to 50% of unexposed controls. Additionally, the immediate increases in cellular NO levels were independent of the function of NO synthase, depended greatly on the substrate source of electrons entering the electron transport chain, and did not result in increased levels of cyclic guanosine monophosphate.Conclusions: Our study concludes the simple model of light-mediated release of NO from COX is unlikely to explain the wide variety of PBM effects reported in the literature. Our multiwavelength method provides a novel tool for studying immediate and early mechanisms of PBM as well as exploring intracellular NO signaling networks.
Highlights
IntroductionPhotobiomodulation (PBM) is an umbrella term for observed beneficial biological effects of low-energy visible to near-infrared (NIR) light absorption.[1,2] PBM has previously been referred to as “laser biostimulation,” “low-level laser therapy,” and “low-level LED therapy,” and typically refers to subthermal red to NIR laser or LED light (though effects in the green and blue wavelength ranges have been reported).[1,2,3,4,5] In contrast to traditional phototherapy, which involves much higher irradiances of UV or full-spectrum light,[6] or photodynamic therapy, which requires the administration of a light-activated exogenous photosensitizer,[7] PBM exposures are low energy and usually involve either laser or very narrowband light sources, and are mediated by photon absorption by purely endogenous cell/tissue components.[1,2,8] Reported therapeutic effects of PBM include enhanced tissue healing,[3,4,9,10] reduction of pain and inflammation,[9,11,12] nerve regeneration,[13,14,15,16,17,18] protection of tissues from poisons of oxidative phosphorylation,[19,20] protection from retinal damage due to high-intensity light or hyperoxia,[21,22,23,24,25,26] and amelioration of symptoms of traumatic brain injury.[27,28,29,30] While there is a rapidly expanding body of published work on these observed benefits, the molecular mechanisms governing the initiation of these effects remain poorly understood
Our study concludes the simple model of light-mediated release of nitric oxide (NO) from c oxidase (COX) is unlikely to explain the wide variety of PBM effects reported in the literature
For over 20 years, COX has been theorized to be the primary chromophore for PBM effects, whereby subsequent NO eviction is the cited mechanism by which light induces changes in mitochondrial function.[1,8,35]
Summary
Photobiomodulation (PBM) is an umbrella term for observed beneficial biological effects of low-energy visible to near-infrared (NIR) light absorption.[1,2] PBM has previously been referred to as “laser biostimulation,” “low-level laser therapy,” and “low-level LED therapy,” and typically refers to subthermal red to NIR laser or LED light (though effects in the green and blue wavelength ranges have been reported).[1,2,3,4,5] In contrast to traditional phototherapy, which involves much higher irradiances of UV or full-spectrum light,[6] or photodynamic therapy, which requires the administration of a light-activated exogenous photosensitizer,[7] PBM exposures are low energy and usually involve either laser or very narrowband light sources, and are mediated by photon absorption by purely endogenous cell/tissue components.[1,2,8] Reported therapeutic effects of PBM include enhanced tissue healing,[3,4,9,10] reduction of pain and inflammation,[9,11,12] nerve regeneration,[13,14,15,16,17,18] protection of tissues from poisons of oxidative phosphorylation,[19,20] protection from retinal damage due to high-intensity light or hyperoxia,[21,22,23,24,25,26] and amelioration of symptoms of traumatic brain injury.[27,28,29,30] While there is a rapidly expanding body of published work on these observed benefits, the molecular mechanisms governing the initiation of these effects remain poorly understood. Downstream effects include increased cellular survival and proliferation,[2,12] increased adenosine triphosphate (ATP) generation,[2,8] and alteration of gene expression.[1,30,31,32,33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
