Light - Various
The applied light's multiple targets and pathways on living systems and its therapeutic use
Applied light of very low intensity (whose effects no depend on heating of tissues) is used in two kind of applications; first as purely experimental approaches in which procedures are developed to show if a specific components of cells is a possible target and what reaction mechanisms are acting, and secondly with therapeutic intention, in more replicated and tested setups, to ameliorate patients symptoms. ...
Much of the used lights in the two cases, but specially in the therapeutic application, is of the red to near-infrared wavelength (>650nm), to review these there is a specific section on this web . Here multi-wavelength studies, or studies that use wavelengths of other spectra of the visible light, are presented.
Respect to the sources that can be used to irradiate biological samples, two major light generator systems are used; Lasers that generate coherent light but are expensive, and light-emitting diode (LED) lights that are much less expensive and that researches are demonstrating that they provoke very similar effects than those produced by laser , the effects of low level light therapy (LLLT) apparently does not depend on coherence, it's therefore possible to achieve photobiostimulation by using non-laser light-generating devices, such as mentioned cheaper LED technology [3,4].
Anyways there can be some slight differences between two systems, in  it has been measured the stimulating effect of different lights on sperm motility and it’s found that the magnitude of the stimulating effect for radiation with natural polarization (LED) is significantly smaller with respect to all the parameters than when radiation with linear polarization (laser) is used. On the contrary in  although both, laser and LED, increases viability of random skin flaps, LED was more effective in increasing the number of mast cells and blood vessels in the transition line of the skin flaps.
A variety of possible therapeutic uses, of light wavelength other than red to infrared (that is more standardized and extended), are nowadays under scrutiny.
For example, in , rats are exposed to different wavelength with blue, green and red LED lights, and is proved that fibroblast cells percentage (involved in collagen production, so also in wound healing) augmented when applied not only red light but also green (530 nm) light. In a similar three wavelengths experiment  it's found also that red and green lights show a potentiation of fibroblast cells (that is measured by means of mRNA and protein levels of cytokines secreted by fibroblasts) and also found that some specific cytokines are significantly increased only by this green light. In another paper  it has been found that 850 nm (near‐infrared) light (20 J/cm2) exerted also a stimulatory metabolic effect in these type of cells (in this case human dermal fibroblast) with no detectable intracellular ROS formation, blue light (450 nm), on the contrary, has been found that has two effects depending on intensity inhibitory at low‐ to mid‐ dose levels (<=30 J/cm2), and cytotoxic at higher dose levels (>30 J/cm2) and that the effect is accompanied by a dose‐dependent release of ROS.
In  it has been found that green light (532nm), and also red light, promote the proliferation of mesenchymal cells, and specifically it’s found that green light inserted a much profound effect at specific dosages than red light. Various differences have been found in another experimental setup with human adipose-derived stem cells where four exposure wavelength are used (blue, green, red and near-infrared) :
" When cultured in proliferation medium there was a clear difference between blue/green which inhibited proliferation and red/NIR which stimulated proliferation, all at 3 J/cm2. Blue/green reduced cellular ATP, while red/NIR increased ATP in a biphasic manner. Blue/green produced a bigger increase in intracellular calcium and reactive oxygen species (ROS). Blue/green reduced mitochondrial membrane potential (MMP) and lowered intracellular pH, while red/NIR had the opposite effect. Transient receptor potential vanilloid 1 (TRPV1) ion channel was expressed in hADSC, and the TRPV1 ligand capsaicin (5uM) stimulated proliferation, which could be abrogated by capsazepine. The inhibition of proliferation caused by blue/green could also be abrogated by capsazepine, and by the antioxidant, N-acetylcysteine. The data suggest that blue/green light inhibits proliferation by activating TRPV1, and increasing calcium and ROS."
In  wavelength dependent NO levels on human retinal pigmented epithelium cells have been found after exposures to 447nm, 532nm, 635nm and 808nm laser lights, additionally:
" ... this wavelength-dependent rise in NO is independent of the function of nitric oxide synthase, and highly dependent on the source of electrons feeding the electron transport chain of the light-exposed cells."
Another kind of therapeutical use is to regulate or inhibit the proliferation of certain bacteria in human hosts, in the case of E.Coli  it has found that 538nm (green) light inhibited proliferation, 590nm (yellow) has no effect, while 610nm (orange), 644nm (red), 464nm (purple) and 453nm (blue) enhanced growth with varying degrees.
Blue light can also have therapeutic uses, however, in  apart from red light (that also is effective) blue light of 470 nm is used to irradiate rodents for 10 min in 5 consecutive days and is found an increased angiogenesis with with significantly improved tissue perfusion and reduced tissue necrosis.
Other kind of therapeutic application of light, application of bright light through ears channels, is oriented to treat brain diseases and there are various positive results such as to treat seasonal affective disorder [10,30] or jet lag symptoms [11,30]. In  transtracranial light illumination thought ears affects the observed molecules involved in circadian rhythmicity (melanopsin and serotonin), in another study  is showed that:
" With extraocular bright light delivery via both ear canals, centro-parietal P300 responds differently toward emotional distractors, indicating that the human brain reacts to extraocular light. The centro-parietal P300 has been associated with attentional resource allocation , with emotional stimuli able to capture attentional resources [19,23,46] and modulate centro-parietal P300 amplitude [41–43]. The emotional modulation of centro-parietal P300 amplitude due to emotional distractors disappeared during extra-ocular light delivery. Thus, extraocular light modulated emotion-attention interaction."
Transcranial light via ear canals also has been show to affects plasma monoamine levels and expression of brain encephalopsin in the mouse .
More invasive is low level laser light application through a transcatheter, a method used to treat Alzheimer  where all test group patients have demonstrated long-lasting positive outcome after the treatment.
Other series of investigation on therapeutic uses of light is oriented to the amelioration of fertility of oocytes or fertilising abilities of sperm . More experimental but remaining in the therapeutic application is an experiment  where biophotons from sperms are measured and digitally stored in computer and later applied to womans that desire to get pregnant after intratubal insemination, achieving 3 more times success cases than controls without treatment. A kind of biophotonic tratment is also used in  during in vitro maturation of ooccites causing a higher (p<0.05) blastocyst formation that improve their developmental competence.
In this sense possibly low level light therapy effect exists because it explodes previously preexistent biophotonic information exchange and generation/reception mechanisms inside cells, although the intensities used on externally applied light is much greater than biophotons emissions detected outside cells or bodies it’s also true that most probably the biophoton activity inside cells is various order of magnitudes greater than outside (see section  for more info about biophotons).
Interesting as supporting material for the main proposition of this web (that is, the electromagnetic nature of mind) are the experimental studies of light radiation on biological samples, specially brains and neurons, because one of the aspects that are differently treated on these experiments with respect to the "therapeutic application" oriented experiments is the theoretical elucidation of what are the possible light targets that later cause all the response cascades, therapeutic investigations are more conservative and often put in the scope various possible biochemical mechanisms like in :
" To date, several mechanisms of biological action have been proposed, although none have been clearly established. These include augmentation of cellular ATP levels [18–20], manipulation of inducible nitric oxide synthase (iNOS) activity [21–25], suppression of inflammatory cytokines, such as TNF-alpha [19,26–28], IL-1beta [28–30], IL-6 [28,31–34] and IL-8 [28,31,32,35], upregulation of growth factors, such as PDGF, IGF-1, NGF and FGF-2 [30,36–38], alteration of mitochondrial membrane potential [39–42], due to chromophores found in the mitochondrial respiratory chain [43–45], stimulation of protein kinase C (PKC) activation , manipulation of NF-kappaB activation , induction of reactive oxygen species (ROS) [48,49], modification of extracellular matrix components , inhibition of apoptosis , stimulation of mast cell degranulation  and upregulation of heat shock proteins ."
But various experimental investigations propose a more extended and systemic target, water, as a main target of light irradiation taking in consideration the properties of coherent domains and exclusion zones in water (see section ) and that incident light has a powerful effect on the size of the interfacial water’s exclusion zone (EZ). In  it's discovered that:
" For UV and visible ranges, all incident wavelengths brought appreciable expansion (Figure 4A). The degree of expansion increased with increasing wavelength, the exception being the data point at 270 nm, which was higher than the local minimum at 300 nm. The higher absorption may reflect the signature absorption peak at 270 nm characteristic of the EZ.18 Clear wavelength sensitivity was also found in the IR region, the most profound expansion occurring at 3.1 µm (Figure 4B). Recognizing that the optical power available for use in the IR region was 1/600 of that in the visible and UV regions, one can assume that with comparable incident power, the IR curve would shift considerably upward—continuing the upward trend evident in Figure 4A. Hence, the most profound effect is in the mid-IR region, particularly at 3.1 µm."
This, at least, can cause variations in the Brownian motion, but here are underpinned theories with more profound implications like that proposed by Santana et al.  where:
" Though existing data have not yet proven the role of EZ water in photobiomodulation, research shows that EZ water can store charge and can later return it in the form of current flow, with as much as 70% of the input charge being readily obtainable. Macroscopic separation of charges can be stable for days to weeks and has unusual electric potential. Water is, thus, an unexpectedly effective charge separation and storage medium."
" EZ may be selectively targeted in photobiomodulation as an efficient energy reservoir, which cells can use expeditiously to fuel cellular work, triggering signaling pathways and gene expression in the presence of injury-induced redox potential."
Externally applied light may target the collective organization of water to influence biomolecules. The section dedicated to the influence of red to near-infrared radiation  explores this evidence more profoundly following various experiments with radiation in those wavelengths. Only to mention here one preliminary evidence of the theory that can be found in .
One of the more striking investigation lines can be the one that study the effects of light applied directly over the skull of the head because it has been found that light could traverse cerebral space and, for example, it can be discerned by photomultipliers at the other side and affect the power of specific bands of quantitative electroencephalographic (EEG) activity on the opposite side of the skull . So, brain function may be modulated by light, specially if the light is patterned with a series of impulses, in  serial 5-min on to 5-min off presentations of patterned blue light resulted in suppression of gamma activity within the right cuneus (including the extrastriate area), altered beta activity within the left angular and right superior temporal regions, and alpha power within the right parahippocampal regions.
To add some adequate perspective to all this and to the sensibility of the brain to light it’s mentionable the discovery that only one photon (in principle through eyes) can affects the brain response .
5. Barulin, Nikolai V., and Vitaly Yu Plavskii. "Effect of Polarization and Coherence of Optical Radiation on Sturgeon Sperm Motility." World Academy of Science, Engineering and Technology, International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering 6.7 (2012): 455-459.
6. de Sousa, Ana Paula Cavalcanti, et al. "Effect of LED phototherapy of three distinct wavelengths on fibroblasts on wound healing: a histological study in a rodent model." Photomedicine and laser surgery 28.4 (2010): 547-552.
7. Fushimi, Tomohiro, et al. "Green light emitting diodes accelerate wound healing: characterization of the effect and its molecular basis in vitro and in vivo." Wound Repair and Regeneration 20.2 (2012): 226-235.
8. Soltani, Samereh Dehghani, et al. "Different effects of energy dependent irradiation of red and green lights on proliferation of human umbilical cord matrix-derived mesenchymal cells." Lasers in medical science 31.2 (2016): 255-261.
11. Jurvelin, Heidi, Jari Jokelainen, and Timo Takala. "Transcranial bright light and symptoms of jet lag: a randomized, placebo-controlled trial." Aerospace medicine and human performance 86.4 (2015): 344-350.
18. Kushibiki, Toshihiro, et al. "Regulation of miRNA expression by low-level laser therapy (LLLT) and photodynamic therapy (PDT)." International journal of molecular sciences 14.7 (2013): 13542-13558.
21. Santana-Blank, Luis, Elizabeth Rodríguez-Santana, and Karin E. Santana-Rodríguez. "Photobiomodulation of aqueous interfaces as selective rechargeable bio-batteries in complex diseases: personal view." Photomedicine and laser surgery 30.5 (2012): 242-249.
22. Rodríguez-Santana, Elizabeth, and Luis Santana-Blank. "Emerging evidence on the crystalline water-light interface in ophthalmology and therapeutic implications in photobiomodulation: first communication." Photomedicine and laser surgery 32.4 (2014): 240-242.
23. Persinger, Michael A., Blake T. Dotta, and Kevin S. Saroka. "Bright light transmits through the brain: Measurement of photon emissions and frequency-dependent modulation of spectral electroencephalographic power." (2013).
24. Karbowski, Lukasz M., et al. "LORETA indicates frequency-specific suppressions of current sources within the cerebrums of blindfolded subjects from patterns of blue light flashes applied over the skull." Epilepsy & Behavior 51 (2015): 127-132.
26. Mignon, Charles, et al. "Differential response of human dermal fibroblast subpopulations to visible and near‐infrared light: Potential of photobiomodulation for addressing cutaneous conditions." Lasers in surgery and medicine (2018)..
27. Wang, Yuguang, et al. "Red (660 nm) or near-infrared (810 nm) photobiomodulation stimulates, while blue (415 nm), green (540 nm) light inhibits proliferation in human adipose-derived stem cells." Scientific reports 7.1 (2017): 7781.
28. Pope, Nathaniel J., Samantha M. Powell, and Jeffrey C. Wigle. "Wavelength dependence of intracellular nitric oxide levels in hTERT-RPE cells in vitro." Mechanisms of Photobiomodulation Therapy XIII. Vol. 10477. International Society for Optics and Photonics, 2018.
29. Azeemi, Samina T. Yousuf, et al. "Effect of visible range electromagnetic radiations on Escherichia coli." African Journal of Traditional, Complementary and Alternative Medicines 14.1 (2017): 24-31.
32. Lee, Joohyeong, et al. "Oocyte maturation under a biophoton generator improves preimplantation development of pig embryos derived by parthenogenesis and somatic cell nuclear transfer." Korean Journal of Veterinary Research 57.2 (2017): 89-95.
Very related sections:
↑ text updated: 04/10/2018
↓ tables updated: 11/04/2019
Applied Fields - Experimental
Light - Various
(F) Full or (A) Abstract
Wavelenght - Intensity
Publication Year (and Number of Pages)
|A||Polarized Polychromatic Noncoherent Light (Bioptron Light) as Adjunctive Treatment in Chronic Oral Mucosal Pain: A Pilot Study||480–3400 nm - (40 mW/cm2)||2019-(1)||Massimo Petruzzi, Gianna Maria Nardi, Fabio Cocco, Fedora della Vella, Roberta Grassi, Felice Roberto Grassi|
|A||Blue light effects in human keloid fibroblasts||-||2019-(1)||Giada Magni, Federica Cherchi, Elisabetta Coppi, Marco Fraccalvieri, Francesca Tatini, Irene Fusco, Roberto Pini, Anna Maria Pugliese, Felicita Pedata, Antongiulio Mangia, Stefano Gasperini, Francesco Pavone, Duccio Rossi Degl'Innocenti, Cristina Tripodi, Domenico Alfieri, Lorenzo Targetti, Francesca Rossi|
|A||Wavelength dependence of intracellular nitric oxide levels in hTERT-RPE cells in vitro||447-808nm||2018-(1)||Nathaniel J. Pope, Samantha M. Powell, Jeffrey C. Wigle|
|F||Transcranial bright light - The effect on human psychophysiology (ear canals)||450-... nm||2018-(92)||Heidi Jurvelin|
|A||Evaluation of fluorescence biomodulation in the real-life management of chronic wounds: the EUREKA trial (fluorescence or biophoton)||-||2018-(1)||Marco Romanelli, Alberto Piaggesi, Giovanni Scapagnini, Valentina Dini, Agata Janowska, Elisabetta Iacopi, Carlotta Scarpa, Stéphane Fauverghe, Franco Bassetto|
|F||EUREKA study - the evaluation of real-life use of a biophotonic system in chronic wound management: an interim analysis (fluorescence or biophoton)||500-610 nm||2017-(8)||Marco Romanelli, Alberto Piaggesi, Giovanni Scapagnini, Valentina Dini, Agata Janowska, Elisabetta Iacopi, Carlotta Scarpa, Stéphane Fauverghe, Franco Bassetto|
|F||Red (660 nm) or near-infrared (810 nm) photobiomodulation stimulates, while blue (415 nm), green (540 nm) light inhibits proliferation in human adipose-derived stem cells||415-810 nm - (15 mW/cm2)||2017-(10)||Yuguang Wang, Ying-Ying Huang, Yong Wang, Peijun Lyu, Michael R. Hamblin|
|F||Oocyte maturation under a biophoton generator improves preimplantation development of pig embryos derived by parthenogenesis and somatic cell nuclear transfer||-||2017-(7)||Joohyeong Lee, Hyeji Shin, Wonyou Lee, Seung Tae Lee, Geun-Shik Lee, Sang-Hwan Hyun, Eunsong Le|
|F||Transcranial Light Alters Melanopsin and Monoamine Production in Mouse (Mus musculus) Brain (ear canals)||450nm - (<14.7 mW/cm2)||2017-(7)||Antti Flyktman, Toni Jernfors, Satu Manttari, Juuso Nissila, Markku Timonen, Seppo Saarela|
|F||Direct detection of a single photon by humans||-||2016-(9)||Jonathan N. Tinsley, Maxim I. Molodtsov, Robert Prevedel, David Wartmann, Jofre Espigulé-Pons, Mattias Lauwers, Alipasha Vaziri|
|F||Human Brain Reacts to Transcranial Extraocular Light (ear canals)||448nm||2016-(12)||Lihua Sun, Jari Peräkylä, Anselmi Kovalainen, Keith H. Ogawa, Pekka J. Karhunen, Kaisa M. Hartikainen|
|A||Green laser light irradiation enhances differentiation and matrix mineralization of osteogenic cells||532nm - 4 J/cm2||2016-(1)||Elisabetta Merigo, Sebastien Bouvet-Gerbettaz, Florian Boukhechba, Jean-Paul Rocca, Carlo Fornaini, Nathalie Rochet|
|F||LORETA indicates frequency-specific suppressions of current sources within the cerebrums of blindfolded subjects from patterns of blue light flashes applied over the skull (transcranial)||470nm - 10000 lux||2015-(6)||Lukasz M. Karbowski, Kevin S. Saroka, Nirosha J. Murugan, Michael A. Persinger|
|F||Transcranial light affects plasma monoamine levels and expression of brain encephalopsin in the mouse (ear canals)||450nm - (<14.7 mW/cm2)||2015-(7)||Antti Flyktman, Satu Mänttäri, Juuso Nissilä, Markku Timonen, Seppo Saarela|
|F||Transcranial bright light exposure via ear canals does not suppress nocturnal melatonin in healthy adults – A single-blind, sham-controlled, crossover trial (ear canals)||450nm - (7.28 mW/cm2)||2014-(6)||Heidi Jurvelin, Timo Takala, Lilli Heberg, Juuso Nissila, Melanie Ruger, Juhani Leppaluoto, Seppo Saarela, Olli Vakkuri|
|F||Emerging Evidence on the Crystalline Water-Light Interface in Ophthalmology and Therapeutic Implications in Photobiomodulation: First Communication (water)||305-400nm - (0.05 mW/cm2)||2014-(2)||Elizabeth Rodríguez-Santana, Luis Santana-Blank|
|F||Bright light transmits through the brain: Measurement of photon emissions and frequency-dependent modulation of spectral electroencephalographic power (transcranial)||10000 lux||2013-(7)||Michael A. Persinger, Blake T. Dotta, Kevin S. Saroka|
|F||Effect of Polarization and Coherence of Optical Radiation on Sturgeon Sperm Motility||420-800nm, 670nm - (1.5 mW/cm2)||2012-(5)||Nikolai V. Barulin, Vitaly Yu. Plavskii|
|F||The effect of biophoton intervention on the pH level of aging milk||-||2010-(59)||Paul Mak|
|F||Effect of Radiant Energy on Near-Surface Water (water)||250-650nm, 1750-4250nm||2009-(13)||Binghua Chai , Hyok Yoo , Gerald H. Pollack|
(F) Full or (A) Abstract
Wavelenght - Intensity
Publication Year (and Number of Pages)
|F||The impact of wavelengths of LED light-therapy on endothelial cells||475-635nm - (40 mW/cm2)||2018-(11)||Sabrina Rohringer, Wolfgang Holnthoner, Sidrah Chaudary, Paul Slezak, Eleni Priglinger, Martin Strassl, Karoline Pill, Severin Mühleder, Heinz Redl, Peter Dunge|
|F||Red (635 nm), Near-Infrared (808 nm) and Violet-Blue (405 nm) Photobiomodulation Potentiality on Human Osteoblasts and Mesenchymal Stromal Cells: A Morphological and Molecular In Vitro Study||405-808nm - 0.4 J/cm2||2018-(23)||Alessia Tani, Flaminia Chellini, Marco Giannelli, Daniele Nosi, Sandra Zecchi-Orlandini, Chiara Sassoli|
|A||Differential response of human dermal fibroblast subpopulations to visible and near-infrared light: Potential of photobiomodulation for addressing cutaneous conditions||450-850nm||2018-(1)||Charles Mignon, Natallia E. Uzunbajakava, Irene Castellano‐Pellicena, Natalia V. Botchkareva, Desmond J. Tobin|
|F||Effect of visible range electromagnetic radiation on Escherichia Coli||464-644nm||2017-(8)||Samina T. Yousuf Azeemi, Saleem Farooq Shaukat, Khawaja Shamsuddin Azeemi, Idrees Khan, Khalid Mahmood, Farah Naz|
|F||Effects of light emitting diode irradiation on neural differentiation of human umbilical cord-derived mesenchymal cells||530-630nm - (5.3 mW/cm2) 0.31-1.59 J/cm2||2017-(9)||Samereh Dehghani-Soltani, Mohammad Shojaee, Mahshid Jalalkamali, Abdolreza Babaee, Seyed Noureddin Nematollahi-Mahani|
|A||Low level lasers effect on proliferation, migration and anti-apoptosis of mesenchymal stem cells||-||2017-(1)||Kan Yin, Rongjia Zhu, Shihua Wang, Robert Chunhua Zhao|
|F||Neuroprotective Effects Against POCD bt Photobiomodulation Evidence from Assembly/Disassembly of the Cytoskeleton||-||2015-(19)||Ann D. Liebert , Roberta T. Cho, Brian t. Bicknell, Euahna Varigos|
|F||Promotion of neural sprouting using low-level green light-emitting diode phototherapy||520nm - (100mW/cm2)||2015-(3)||Noa Alon, Hamootal Duadi, Ortal Cohen, Tamar Samet, Neta Zilony, Hadas Schori, Orit Shefi, Zeev Zalevsky|
|F||Different effects of energy dependent irradiation of red and green lights on proliferation of human umbilical cord matrix-derived mesenchymal cell||532nm, 630nm - 0.31-12.72 J/cm2||2015-(7)||Samereh Dehghani Soltani, Abdolreza Babaee, Mohammad Shojaei, Parvin Salehinejad, Fatemeh Seyedi, Mahshid JalalKamali, Seyed Noureddin Nematollahi-Mahani|
|A||Low level light therapy by LED of different wavelength induces angiogenesis and improves ischemic wound healing||470nm, 629nm - (50 mW/cm2)||2014-(1)||P. Dungel, J. Hartinger, S. Chaudary, P. Slezak, A. Hofmann, T. Hausner, M. Strassl, E. Wintner, H. Redl, R. Mittermayr|
|F||Transcranial bright light treatment via the ear canals in seasonal affective disorder: a randomized, double-blind dose-response study (ear canals)||448nm - 2386 lux (0.72 mW/cm2), 9542 lux (2.88 mW/cm2), 21470 lux (6.48 mW/cm2)||2014-(11)||Heidi Jurvelin, Timo Takala, Juuso Nissilä, Markku Timonen, Melanie Rüger, Jari Jokelainen, Pirkko Räsänen|
|F||Biophotonic energy in an intratubal insemination program||-||2013-(4)||G.Menaldo, S.Serrano, S.Benvenuto, B.Lopez|
|A||Green light emitting diodes accelerate wound healing: Characterization of the effect and its molecular basis in vitro and in vivo||456nm, 518nm, 456nm||2012-(1)|
|A||Effect of LED phototherapy of three distinct wavelengths on fibroblasts on wound healing: a histological study in a rodent model||460nm, 530nm, 700nm - 10 J/cm2||2010-(1)||A.P.C. de Sousa, J.N. Santos, J.A. dos Reis Jr, T.A. Ramos, J. de Souza, M.C.T. Cangussú, A.L. Pinheiro|