Part One of this series reviewed the mechanism of how low level lasers interact at the cellular level . The coherent laser light in the near infrared wavelength is absorbed readily by cytochrome C oxidase located in the inner mitochondrial membrane. This is thought to be an ancient remnant of the ability of photosynthetic bacteria to absorb light and convert it into usable energy for cellular use.
Above left image: Mitochondria with illuminated inner membrane. This is the location of Cytochrome C oxidase which absorbs the red light.
EndoSymbiotic Theory of Lynn Margulis
Where did mitochondria come from?
One theory is that mitochondria originated from the bacterial world, incorporated into multicelled organisms in a symbiotic relationship. This idea was proposed as the endosymbiotic theory by Lynn Margulis, a biologist at Berkely in her 1970 book, the Origin of Eucaryotic Cells (1) . This explains why the primitive mechanism for light absorption is retained by our mitochondria.
Accelerated Wound Healing
A 2004 paper by Dr Janis T. Eellsa appeared in Mictochondrion stating that mitochondrial
signal transduction accelerates wound and retinal healing by
near-infrared light therapy. The authors state, "Photobiomodulation
by light in the red to near infrared range (630–1000 nm) using low
energy lasers or light-emitting diode (LED) arrays has been shown to
accelerate wound healing, improve recovery from ischemic injury in the
heart and attenuate degeneration in the injured optic nerve. Recent
evidence indicates that the therapeutic effects of red to near infrared
light result, in part, from intracellular signaling mechanisms triggered
by the interaction of NIR light with the mitochondrial photoacceptor
molecule cytochrome c oxidase.
We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice
by upregulating genes important in the promotion of wound healing.
Upregulates Gene Expression
Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression
in pathways involved in mitochondrial energy production and antioxidant
cellular protection. These findings provide a link between the actions
of red to near infrared light on mitochondrial oxidative metabolism in
vitro and cell injury in vivo.
Based on these findings and the strong
evidence that mitochondrial dysfunction is involved in the
pathogenesis of numerous diseases processes, we propose that NIR-LED
photobiomodulation represents an innovative and non-invasive therapeutic
approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber’s hereditary optic neuropathy and Parkinson’s disease." (2)
What Happens After the Coherent Light is Absorbed by the Mitochondria?
Not only is light energy utilized in the production of ATP (usable cellular energy), the light energy triggers a cascade which initiates the healing process.
Low Level Laser light
accelerates wound healing, provides pain relief, improves the immune
system and helps nerve regeneration. Low-energy coherent light in the
red and infra-red range activates the mitochondrial respiratory chain
components, and initiates a signaling cascade that promotes healing, and
new cell growth. Cytochrome C oxidase is the molecule which absorbs
the light in the inner membrane of the mitochondria. This protein
contains four active metal centers, two iron and two copper molecules,
which absorb light, thereby increasing mitochondrial respiration and ATP
Clinical Conditions Which Benefit from Coherent Light, (LLLT) Low Level Laser Therapy
Wound Healing (9) Animal studies show light-dose dependent increase in collagen levels during the post-wounding days. The histological examination show significant
increase in collagen deposition along with the reduced edema,
leukocytes, increased granulation tissue, and fibroblast number in the
optimal laser dose treated group compared to the non-illuminated
Conclusion Low level laser is an excellent method for healing sports injuries, the musclo-tendinous system. In addition there are multiple clinicial applications for healing the nervous system, intractable nerve pain, chronic viral illness (herpes) and fungal illnes (nail fungus). The future of this modality is indeed very bright.(10) Low level laser is an emerging clincical paradigm. (12) Dr Huang and Hamblin conclude with this: " LLLT is used by physical therapists, dentists, dermatologists, rheumatologists, and other specialists, as well as general practitioners. Laser therapy is also widely used in veterinary and sports medicine, and in rehabilitation clinics. Ongoing preclinical studies and clinical trials are using LLLT to treat serious and potentially fatal injuries and diseases including heart attacks and coronary artery disease, nerve regeneration and spinal cord injury, stroke, traumatic brain injuries, and degenerative neurological disorders such as Alzheimer's and Parkinson's diseases. (12)
ENDOSYMBlOTlC THEORY - Evolutionist Lynn Margulis showed that a major organizational event in the history of life probably involved the merging of two or more lineages through symbiosis. Lynn Margulis Symbiotic microbes = eukaryote cells? Mitochondria, for example, are wriggly bodies that generate the energy required for metabolism. To Margulis, they looked remarkably like bacteria.
"She knew that scientists had been struck by the similarity ever since the discovery of mitochondria at the end of the 1800s. Some even suggested that mitochondria began from bacteria that lived in a permanent symbiosis within the cells of animals and plants. There were parallel examples in all plant cells. Algae and plant cells have a second set of bodies that they use to carry out photosynthesis. Known as chloroplasts, they capture incoming sunlight energy. The energy drives biochemical reactions including the combination of water and carbon dioxide to make organic matter. Chloroplasts, like mitochondria, bear a striking resemblance to bacteria. Scientists became convinced that chloroplasts (below right), like mitochondria, evolved from symbiotic bacteria — specifically, that they descended from cyanobacteria (above right), the light-harnessing small organisms that abound in oceans and fresh water. When one of her professors saw DNA inside chloroplasts, Margulis was not surprised. After all, that's just what you'd expect from a symbiotic partner. Margulis spent much of the rest of the 1960s honing her argument that symbiosis (see figure, below) was an unrecognized but major force in the evolution of cells. In 1970 she published her argument in The Origin of Eukaryotic Cells. "
(2) http://www.lighttherapysystems.eu/images/AcceleratedHealing.pdf Mitochondrion 4 (2004) 559–567 Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. by Janis T. Eellsa,*, Margaret T.T. Wong-Rileyb, James VerHoevec, Michele Henryd, Ellen V. Buchmane, Mary P. Kanee, Lisa J. Gouldf, Rina Dasg, Marti Jettg, Brian D. Hodgsonh, David Margolisi, Harry T. Whelane aDepartment of Health Sciences, College of Health Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA bDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53201, USA
Photobiomodulation by light in the red to near infrared range (630–1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase.
We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors.
We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients.
Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing.
More recent studies have provided evidence for the therapeutic benefit of NIRLED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication.
Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber’s hereditary optic neuropathy and Parkinson’s disease.
(3) http://www.ncbi.nlm.nih.gov/pubmed/9892822 Forsch Komplementarmed. 1998;5(5):244-247. Healing of Bone Affections and Gangrene with Low-Intensity Laser Irradiation in Diabetic Patients Suffering from Foot Infections. Schindl M, Schindl A, Pölzleitner D, Schindl L.
Two consecutive diabetic male patients with gangrene, osteomyelitis, and bone fractures. Helium-neon laser irradiation (36 J/cm2 ) 50 min/day. MAIN OUTCOME PARAMETER: Healing of gangrene and corticalis lesion as well as remineralisation of bone affections. Within a mean period of 14 weeks not only a complete healing of the diabetic gangrenes but also a radiographically determined reestablishment of corticalis and remineralisation of preexisting bone affections could be achieved. CONCLUSION: We therefore conclude that low-intensity laser irradiation should be further tested as an additional beneficial therapeutic modality for the healing of gangrene and bone affections in diabetic patients.
Photomed Laser Surg. 2011 Nov 2. [Epub ahead of print] The Effect of 670-nm Low Laser Therapy on Herpes Simplex Type 1. Muñoz Sanchez PJ, Capote Femenías JL, Díaz Tejeda A, Tunér J. Source 1 Leonardo Fernández Sánchez Dental Clinic , Cienfuegos, Cuba . Abstract
Abstract Objective: The purpose of this work was to study the effect of low-level laser therapy (LLLT) on the healing and relapse intervals in patients with recurrent labial herpes simplex infections. Background data: Several pharmaceuticals are available to reduce symptoms and improbé healing of labial herpes, but only LLLT has been reported to significantly influence the length of the recurrence period. Material and methods: In an initial study, 232 patients with herpes simplex type 1 virus symptoms were consecutively selected for either LLLT or conventional therapy, including acyclovir cream or tablets. One of the dentists was responsible for the diagnosis, a second dentist for the treatment, and and a third for the evaluation, to allow for a semi-blinded procedure. Patients in the laser group received 670-nm laser irradiation, 40 mW, 1.6 J, 2.04 J/cm(2), 51 mW/cm(2) per blister in the prodromal stage and 4.8 J in the crust and secondarily infected stages, plus 1.2 J at the C2-C3 vertebrae. Patients were monitored daily during the first week to control healing, and monthly for 1 year to check on recurrence. In a consecutive study, 322 patients receiving LLLT were followed during 5 years to observe the period of ocurrences.
Results: An obvious effect of LLLT was found for both initial healing and for the length of the recurrence periods. Conclusions: LLLTof herpes simples virus 1 (HSV-1) appears to be an effective treatment modality without any observed side effects.
Herpes Zoster (Shingles): A Therapy at Last November 2005
Low Intensity Laser Therapy when properly applied has an infinite ability to heal. Along with a number of systemic, dermatological and musculoskeletal problems, we may be able to now add shingles to the list of conditions where Low Intensity Laser Therapy may be applied as an effective therapy. Over the past two years at our rehabilitation centre, we have treated a number of patients afflicted with this sometimes severe viral infection and have been universally successful in treating these conditions. Excellent Before and After Treatment Photos showing resolution of lesions.
Support Care Cancer. 2011 Aug;19(8):1069-77. Epub 2011 Jun 10. A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis. Bjordal JM, Bensadoun RJ, Tunèr J, Frigo L, Gjerde K, Lopes-Martins RA. Centre for Evidence-Based Practice, Bergen University College-HiB, Moellendalsvn. 6, 5009, Bergen, Norway.
The purpose of this study is to review the effects of low-level laser therapy (LLLT) in the prevention and treatment of cancer therapy-induced oral mucositis (OM). METHODS: A systematic review and meta-analysis of randomised placebo-controlled trials of LLLT performed during chemotherapy or radiation therapy in head and neck cancer patients. We found 11 randomised placebo-controlled trials with a total of 415 patients; methodological quality was acceptable at 4.10 (SD ± 0.74) on the 5-point Jadad scale. The relative risk (RR) for developing OM was significantly (p = 0.02) reduced after LLLT compared with placebo LLLT (RR = 2.03 (95% CI, 1.11 to 3.69)). This preventive effect of LLLT improved to RR = 2.72 (95% CI, 1.98 to 3.74) when only trials with adequate doses above 1 J were included. For treatment of OM ulcers, the number of days with OM grade 2 or worse was significantly reduced after LLLT to 4.38 (95% CI, 3.35 to 5.40) days less than placebo LLLT. Oral mucositis severity was also reduced after LLLT with a standardised mean difference of 1.33 (95% CI, 0.68 to 1.98) over placebo LLLT. All studies registered possible side-effects, but they were not significantly different from placebo LLLT.
CONCLUSIONS: There is consistent evidence from small high-quality studies that red and infrared LLLT can partly prevent development of cancer therapy-induced OM. LLLT also significantly reduced pain, severity and duration of symptoms in patients with cancer therapy-induced OM.
(7) http://www.ncbi.nlm.nih.gov/pubmed/21910734 Photochem Photobiol. 2011 Nov-Dec;87(6):1447-52. doi: 10.1111/j.1751-1097.2011.00999.x. Epub 2011 Oct 7. Infrared (810 nm) low-level laser therapy in rat achilles tendinitis: a consistent alternative to drugs. by Marcos RL, Leal Junior EC, Messias Fde M, de Carvalho MH, Pallotta RC, Frigo L, dos Santos RA, Ramos L, Teixeira S, Bjordal JM, Lopes-Martins RÁ. Source : Laboratory of Pharmacology and Experimental Therapeutics, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP-Brazil.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used and can reduce musculoskeletal pain in spite of the cost of adverse reactions like gastrointestinal ulcers or cardiovascular events. The current study investigates if a safer treatment such as low-level laser therapy (LLLT) could reduce tendinitis inflammation, and whether a possible pathway could be through inhibition of either of the two-cyclooxygenase (COX) isoforms in inflammation. Wistar rats (six animals per group) were injected with saline (control) or collagenase in their Achilles tendons. Then, we treated them with three different doses of IR LLLT (810 nm; 100 mW; 10 s, 30 s and 60 s; 3.57 W cm(-2); 1 J, 3 J, 6 J) at the sites of the injections, or intramuscular diclofenac, a nonselective COX inhibitor/NSAID. We found that LLLT dose of 3 J significantly reduced inflammation through less COX-2-derived gene expression and PGE(2) production, and less edema formation compared to nonirradiated controls. Diclofenac controls exhibited significantly lower PGE(2) cytokine levels at 6 h than collagenase control, but COX isoform 1-derived gene expression and cytokine PGE(2) levels were not affected by treatments. As LLLT seems to act on inflammation through a selective inhibition of the COX-2 isoform in collagenase-induced tendinitis, LLLT may have potential to become a new and safer nondrug alternative to coxibs.
(8) http://www.ncbi.nlm.nih.gov/pubmed/22009383 Lasers Med Sci. 2011 Oct 19. [Epub ahead of print] Low-level laser therapy improves repair following complete resection of the sciatic nerve in rats. Medalha CC, Di Gangi GC, Barbosa CB, Fernandes M, Aguiar O, Faloppa F, Leite VM, Renno AC. Source Department of Bioscience, Federal University of São Paulo (UNIFESP), Avenida Ana Costa 95, CEP 04021-001, Santos, SP, Brazil,
The aim of this study is to analyze the effects of low-level laser therapy (LLLT) on the regeneration of the sciatic nerve in rats following a complete nerve resection. Male Wistar rats were divided into a control injury group, injury groups irradiated with a 660-nm laser at 10 or 50 J/cm(2), and injury groups irradiated with an 808-nm laser at 10 or 50 J/cm(2). Treatment began 24 h following nerve resection and continued for 15 days. Using the sciatic functional index (SFI), we show that the injured animals treated with 660 nm at 10 and 50 J/cm(2) had better SFI values compared with the control injury and the 808-nm groups. Animals irradiated with the 808-nm laser at 50 J/cm(2) show higher values for fiber density than do control animals. In addition, axon and fiber diameters were larger in animals irradiated with 660 nm at 50 J/cm(2) compared to the control group. These findings indicate that 660-nm LLLT is able to provide functional gait recovery and leads to increases in fiber diameter following sciatic nerve resection.
J Biophotonics. 2011 Dec 15. doi: 10.1002/jbio.201100089. [Epub ahead of print] Spectroscopic and histological evaluation of wound healing progression following Low Level Laser Therapy (LLLT). Prabhu V, Rao SB, Chandra S, Kumar P, Rao L, Guddattu V, Satyamoorthy K, Mahato KK . Biophysics Unit, Manipal Life Sciences Centre, Manipal University, Manipal 576104, Karnataka, India.
The present study focuses on the evaluation of the effect of He-Ne laser on tissue regeneration by monitoring collagen synthesis in wound granulation tissues in Swiss albino mice using analysis of laser induced fluorescence (LIF) and light microscopy techniques.
The spectral analyses of the wound granulation tissues have indicated a dose dependent increase in collagen levels during the post-wounding days. The histological examinations on the other hand have also shown a significant increase in collagen deposition along with the reduced edema, leukocytes, increased granulation tissue, and fibroblast number in the optimal laser dose treated group compared to the non-illuminated controls.
(10) Lasers From Head to Toe http://www.pharmacytimes.com/publications/issue/2011/May2011/Lasers-from-Head-to-Toe-Will-New-Procedures-Change-the-Face-of-Pharmacy-
Lasers from Head to Toe: Will New Procedures Change the Face of Pharmacy? Published Online: Monday, May 16th, 2011 Jeannette Y. Wick, RPh, MBA, FASCP
(11) Acne http://www.ncbi.nlm.nih.gov/pubmed/10809858 Br J Dermatol. 2000 May;142(5):973-8. Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris. Papageorgiou P, Katsambas A, Chu A. Source Unit of Dermatology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K. Abstract
In this study we have evaluated the use of blue light (peak at 415 nm) and a mixed blue and red light (peaks at 415 and 660 nm) in the treatment of acne vulgaris. One hundred and seven patients with mild to moderate acne vulgaris were randomized into four treatment groups: blue light, mixed blue and red light, cool white light and 5% benzoyl peroxide cream. Subjects in the phototherapy groups used portable light sources and irradiation was carried out daily for 15 min. Comparative assessment between the three light sources was made in an observer-blinded fashion, but this could not be achieved for the use of benzoyl peroxide. Assessments were performed every 4 weeks. After 12 weeks of active treatment a mean improvement of 76% (95% confidence interval 66-87) in inflammatory lesions was achieved by the combined blue-red light phototherapy; this was significantly superior to that achieved by blue light (at weeks 4 and 8 but not week 12), benzoyl peroxide (at weeks 8 and 12) or white light (at each assessment). The final mean improvement in comedones by using blue-red light was 58% (95% confidence interval 45-71), again better than that achieved by the other active treatments used, although the differences did not reach significant levels. We have found that phototherapy with mixed blue-red light, probably by combining antibacterial and anti-inflammatory action, is an effective means of treating acne vulgaris of mild to moderate severity, with no significant short-term adverse effects.
(12) http://spie.org/x35504.xml?ArticleID=x35504 Biomedical Optics & Medical Imaging. Low-level laser therapy: an emerging clinical paradigm. Ying-Ying Huang, Michael Hamblin, and Aaron C.-H. Chen Improved understanding of the fundamental cellular and molecular mechanisms is broadening the technique's mainstream use for many ailments. 9 July 2009, SPIE Newsroom. DOI: 10.1117/2.1200906.1669
Cytochrome c oxidase is a photoacceptor, absorbing light
at a peak spectrum of 630-670nm (red spectrum). This particular molecule is responsible for ensuring that the Respiratory Chain goes
to completion. The Respiratory Chain harvests electrons from O2 and NADH passing them along through a series of Redox reactions,
ultimately producing ATP and H2O. Cytochrome c oxidase promotes the electron flow along the Respiratory Chain between Complexes III
Chemical & Engineering News
March 19, 2007 Volume 85, Number 12 p. 13
Enzyme Catalysis Electron-Starved Enzyme
Cytochrome c oxidase model mimics natural electron-limited conditions
SChematic model of cytochrome C oxidase
Abstracts The number of positive peer-reviewed publications which support the application of Laser Therapy continues to grow. Meditech
has selected a number of abstracts from these publications and have grouped them by pathology for your review. We regularly update the
abstracts as they become available with the intention of keeping you informed on current research findings.
The Lancet, Volume 374, Issue 9705, Pages 1897 - 1908, 5 December 2009
Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or
active-treatment controlled trials
Dr Roberta T Chow MBBS a Corresponding AuthorEmail Address, Prof Mark I Johnson PhD b, Prof Rodrigo AB Lopes-Martins PhD c, Prof Jan M
Bjordal PT d e
Neck pain is a common and costly condition for which pharmacological management has limited evidence of efficacy and side-effects.
Low-level laser therapy (LLLT) is a relatively uncommon, non-invasive treatment for neck pain, in which non-thermal laser irradiation
is applied to sites of pain. We did a systematic review and meta-analysis of randomised controlled trials to assess the efficacy of
We searched computerised databases comparing efficacy of LLLT using any wavelength with placebo or with active control in acute or
chronic neck pain. Effect size for the primary outcome, pain intensity, was defined as a pooled estimate of mean difference in change
in mm on 100 mm visual analogue scale.
We identified 16 randomised controlled trials including a total of 820 patients. In acute neck pain, results of two trials showed a
relative risk (RR) of 1·69 (95% CI 1·22—2·33) for pain improvement of LLLT versus placebo. Five trials of chronic neck pain reporting
categorical data showed an RR for pain improvement of 4·05 (2·74—5·98) of LLLT. Patients in 11 trials reporting changes in visual
analogue scale had pain intensity reduced by 19·86 mm (10·04—29·68). Seven trials provided follow-up data for 1—22 weeks after
completion of treatment, with short-term pain relief persisting in the medium term with a reduction of 22·07 mm (17·42—26·72). Side-
effects from LLLT were mild and not different from those of placebo.
We show that LLLT reduces pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in
patients with chronic neck pain.
Comparison between Wound Healing in Induced Diabetic and Non diabetic Rats after Low-Level Laser Therapy Aug 2006, Vol. 24, No. 4:
474-479 Sylvia Bicalho Rabelo , D.D.S., M.S.D. Instituto de Pesquisa e Desenvolvimento (IP&D), Universidade do Vale do Paraiba
Systemic Eﬀects of Low-Intensity Laser Irradiation on Skin Micro circulation in Patients with Diabetic Microangiopathy. Andreas
Schindl, Georg Heinze, Martin Schindl, Heidemarie Pernerstorfer-Schönd and Liesbeth Schindl. Microvascular Research Volume 64, Issue
2, September 2002, Pages 240-246
Eﬀects of near-infrared low-level laser irradiation on micro circulation. Yasuyo Maegawa, MD, Toshiyuki Itoh, MD, PhD, Toyoshi
Hosokawa, MD, PhD, Kazuhiro Yaegashi, MD, PhD, Mayumi Nishi, MD, PhD. Lasers in Surgery and Medicine Volume 27 Issue 5, Pages 427 –
Symptomatic Reversal of Peripheral Neuropathy in Patients with Diabetes. Alan B. Kochman, Dale H. Carnegie, and Thomas J. Burke.
Journal of the American Podiatric Medical Association Volume 92 Number 3 125-130 2002
Low-intensity light therapy: exploring the role of redox mechanisms.
Tafur J, Mills PJ.
Department of Psychiatry, Behavioral Medicine Laboratory, University of California at San Diego, La Jolla, California 92093-0804, USA.
Low-intensity light therapy (LILT) appears to be working through newly recognized photoacceptor systems. The mitochondrial electron
transport chain has been shown to be photosensitive to red and near-infrared (NIR) light. Although the underlying mechanisms have not
yet been clearly elucidated, mitochondrial photostimulation has been shown to increase ATP production and cause transient increases in
reactive oxygen species (ROS). In some cells, this process appears to participate in reduction/oxidation (redox) signaling. Redox
mechanisms are known to be involved in cellular homeostasis and proliferative control. In plants, photostimulation of the analogous
photosynthetic electron transport chain leads to redox signaling known to be integral to cellular function. In gene therapy research,
ultraviolet lasers are being used to photostimulate cells through a process that also appears to involve redox signaling. It seems
that visible and near visible low-intensity light can be used to modulate cellular physiology in some nonphotosynthetic cells, acting
through existing redox mechanisms of cellular physiology. In this manner, LILT may act to promote proliferation and/or cellular
homeostasis. Understanding the role of redox state and signaling in LILT may be useful in guiding future therapies, particularly in
conditions associated with pro-oxidant conditions.
J Biomed Sci. 2009 Jan 12;16:4.
Molecular mechanisms of cell proliferation induced by low power laser irradiation.
Gao X, Xing D.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, PR China.
Low power laser irradiation (LPLI) promotes proliferation of multiple cells, which (especially red and near infrared light) is mainly
through the activation of mitochondrial respiratory chain and the initiation of cellular signaling. Recently, the signaling proteins
involved in LPLI-induced proliferation merit special attention, some of which are regulated by mitochondrial signaling. Hepatocyte
growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced
proliferation, but tumor necrosis factor alpha (TNF-alpha) receptor has not been affected. Activated TPKR could activate its
downstream signaling elements, like Ras/Raf/MEK/ERK, PI3K/Akt/eIF4E, PI3K/Akt/eNOS and PLC-gamma/PKC pathways. Other two pathways,
DeltaPsim/ATP/cAMP/JNK/AP-1 and ROS/Src, are also involved in LPLI-induced proliferation. LPLI-induced cell cycle progression can be
regulated by the activation or elevated expressions of cell cycle-specific proteins. Furthermore, LPLI induces the synthesis or
release of many molecules, like growth factors, interleukins, inflammatory cytokines and others, which are related to promotive
effects of LPLI.
Specific helium-neon laser sensitivity of the purified cytochrome c oxidase.
Pastore D, Greco M, Passarella S.
Dipartimento di Scienze Animali, Vegetali e dell'Ambiente, Università del Molise, Campobasso, Italy.
In order to gain some insight into the mechanism of interaction between Helium-Neon (He-Ne) laser light and mitochondrial cytochromes,
the sensitivity of cytochrome electron transfer activity to He-Ne laser was tested.
MATERIALS AND METHODS:
Irradiation of solutions containing either purified cytochromes or dissolved rat liver mitochondria was carried out (wavelength 632.8
nm, fluence rate 10 mW cm(-2), fluence 2 J cm(-2)); the irradiation conditions were the ones able to affect cytochrome c oxidase (COX)
activity in mitochondria (Pastore et al., 1994).
Cytochrome c oxidation catalysed by COX was affected by He-Ne laser irradiation of the purified enzyme. This result was obtained from
measurements of the pseudo-first-order kinetic constant and from determinations of the turnover number of the enzyme, performed at
different cytochrome c/COX ratios. Consistently, the kinetic parameters of COX changed. On the contrary, no alteration in the rate of
electron transfer catalysed by either cytochrome c or bc1 complex was found.
This study shows that purified COX is a specific target of He-Ne laser light; therefore, COX may be considered to be a mitochondrial
Box 1 | The role of cytochrome c in respiration
From the following article Cytochrome c: functions beyond respiration
Yong-Ling P. Ow, Douglas R. Green, Zhenyue Hao & Tak W. Mak
Nature Reviews Molecular Cell Biology 9, 532-542 (July 2008)
One of the essential molecules of the electron-transport chain is cytochrome c (grey circle). Cytochrome c accepts electrons from
Complex III and diffuses to Complex IV (cytochrome oxidase), where it donates the electrons to O2, converting O2 to H2O. Cytochrome c
first forms as apocytochrome c, which is produced by translation and co-translational modification in the cytosol. Apocytochrome c
then translocates to the mitochondrial intermembrane space where the haem moiety is covalently attached by cytochrome c haem lyase to
form holocytochrome c. Concurrently, the partially extended conformation of apocytochrome c becomes the more compact structure of
The electron transport chain consists of 3 complexes of integral membrane proteins
the NADH dehydrogenase complex (I)
the cytochrome c reductase complex (III)
the cytochrome c oxidase complex (IV)
and two freely-diffusible molecules
that shuttle electrons from one complex to the next.
The electron transport chain accomplishes:
the stepwise transfer of electrons from NADH (and FADH2) to oxygen molecules to form (with the aid of protons) water molecules
(Cytochrome c can only transfer one electron at a time, so cytochrome c oxidase must wait until it has accumulated 4 of them
before it can react with oxygen.)
harnessing the energy released by this transfer to the pumping of protons (H+) from the matrix to the intermembrane space.
Approximately 20 protons are pumped into the intermembrane space as the 4 electrons needed to reduce oxygen to water pass through
the respiratory chain.
The gradient of protons formed across the inner membrane by this process of active transport forms a miniature battery.
The protons can flow back down this gradient, reentering the matrix, only through another complex of integral proteins in the
inner membrane, the ATP synthase complex (as we shall now see).
The energy released as electrons pass down the gradient from NADH to oxygen is harnessed by three enzyme complexes of the respiratory
chain (I, III, and IV) to pump protons (H+) against their concentration gradient from the matrix of the mitochondrion into the
intermembrane space (an example of active transport).
As their concentration increases there (which is the same as saying that the pH decreases), a strong diffusion gradient is set up. The
only exit for these protons is through the ATP synthase complex. As in chloroplasts, the energy released as these protons flow down
their gradient is harnessed to the synthesis of ATP.
Why do mitochondria have their own genome?
Many of the features of the mitochondrial genetic system resemble those found in bacteria. This has strengthened the theory that
mitochondria are the evolutionary descendants of a bacterium that established an endosymbiotic relationship with the ancestors of
eukaryotic cells early in the history of life on earth. However, many of the genes needed for mitochondrial function have since moved
to the nuclear genome.
The recent sequencing of the complete genome of Rickettsia prowazekii has revealed a number of genes closely related to those found in
mitochondria. Perhaps rickettsias are the closest living descendants of the endosymbionts that became the mitochondria of eukaryotes.
Chemical & Engineering News. March 19, 2007 Volume 85, Number 12 p. 13
Enzyme Catalysis Electron-Starved Enzyme Cytochrome c
oxidase model mimics natural electron-limited conditions SChematic model
of cytochrome C oxidase
Intracellular ATP level increases in lymphocytes irradiated
with infrared laser light of wavelength 904 nm.
Benedicenti S, Pepe IM, Angiero F, Benedicenti A.
Department of Medical Science, Dentistry, and Biophysics,
University of Genoa, Milan, Italy. firstname.lastname@example.org
Red and near-infrared laser irradiation is reported to have a
range of biological effects on cultured cells and different tissues,
leading to the hypothesis that laser light can affect energy metabolism.
Increased adenosine triphosphate (ATP) synthesis has been
reported in cultured cells and rat brain tissue after irradiation at
632.8 nm and 830 nm, respectively. This study investigated whether diode
pulsed laser irradiation enhances ATP production in lymphocytes.
MATERIALS AND METHODS:
Aliquots (500 microL) of an extract of cultured lymphocytes
of the Molt-4 cell line were irradiated with diode laser light (lambda =
904 nm, pulsed mode, 6 kHz frequency) with an average emission power of
10 mW for 60 min. A Spectra Physics M404 power meter was used to
measure light intensity. Controls were treated similarly but not
irradiated. The amount of ATP was measured by the luciferin-luciferase
The amount of ATP in irradiated cell cultures was 10.79 +/- 0.15 microg/L (SD; n = 10), and in non-irradiated cell cultures it was 8.81 +/- 0.13 microg/L (SD; n = 10).
The average percentage increase of irradiated versus control cell cultures was about 22.4% +/- 0.56% SD (p < 0.001).
This significant increase is probably due to laser
irradiation; it cannot be attributed to any thermal effect, as the
temperature during irradiation was maintained at 37.0 degrees +/- 0.5
degrees C. Thus the therapeutic effects of the biostimulating power of
this type of laser are identified and its indications may be expanded.
Increases nitric oxide
Role of nitric oxide in the visible light-induced
rapid increase of human skin microcirculation at the local and systemic
levels: II. healthy volunteers.
Samoilova KA, Zhevago NA, Petrishchev NN, Zimin AA.
Institute of Cytology, Russian Academy of Sciences, St.
Petersburg, Russia. email@example.com
The aim of this study is to evaluate the skin
microcirculation increase seen in healthy volunteers after a single
exposure to polychromatic visible (pVIS) light, and to prove the role of
nitric oxide (NO) in the development of this effect.
Improvement of microcirculation is one of the most
important effects of laser and pVIS light therapy; however, its
mechanism of action remains unknown. A main role in the regulation of
vascular tone is known to be played by NO. It is produced by NO-synthase
(NOS) located in membranes of many cells, including endothelial and
blood cells. NOS, a biopteroflavohemoprotein, absorbs pVIS light,
resulting in its activation.
MATERIALS AND METHODS:
The central area of the dorsal side of the right hand (24
cm2) of 42 volunteers was irradiated for 5 min with pVIS light from a
Q-light (385-750 nm, 95% polarization, 40 mW/cm2, 12 J/cm2). Then for 90
min, the blood flow rate (Qas) was measured eight times, both in the
area of the irradiation (local effect) and in the non-irradiated left
hand (systemic effect) by using a high-frequency ultrasound Doppler
device, recording Qas in human skin to a depth up to 5 mm. In the
central area of the right hand of 14 volunteers an NOS inhibitor,
N-monomethyl-L-arginine (L-NMMA, 0.1% solution), was iontophoretically
administered prior to exposure, whereas in 10 other subjects it was
administered to the left hand with subsequent exposure of the right
As soon as 2 min after exposure, Qas in the irradiated area
rose on average by 32%, and in 20 min by 45%; it then decreased and in
90 min returned to the initial level. A statistically significant Qas
increase in the non-irradiated hand was recorded in 5 min (+9%), and in
20 min it reached a maximum level (+39%), and 90 min later it decreased
to the initial values. The presence of L-NMMA in the light-exposed area
completely blocked the photoinduced rise of microcirculation, both in
the irradiated and in non-irradiated hand; however, its administration
to the non-irradiated hand did not prevent these effects.
The increase in skin microcirculation produced by pVIS light at the local and systemic levels is due to activation of NO synthesis in the irradiated area.
full text Free
Mechanism of Benefits of Low Level Lasers-
Activates Mitochondrial respiration-
Low-level laser therapy activatesNF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts.
Chen AC, Arany PR, Huang YY, Tomkinson EM, Sharma SK,
Kharkwal GB, Saleem T, Mooney D, Yull FE, Blackwell TS, Hamblin MR.
Wellman Center for Photomedicine, Massachusetts General
Hospital, Boston, Massachusetts, United States of America.
Despite over forty years of investigation on low-level light
therapy (LLLT), the fundamental mechanisms underlying
photobiomodulation at a cellular level remain unclear.
In this study, we isolated murine embryonic fibroblasts
(MEF) from transgenic NF-kB luciferase reporter mice and studied their
response to 810 nm laser radiation. Significant activation of NF-kB was
observed at fluences higher than 0.003 J/cm(2) and was confirmed by
Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT
compared to conventional lipopolysaccharide treatment. We also observed
that LLLT induced intracellular reactive oxygen species (ROS) production
similar to mitochondrial inhibitors, such as antimycin A, rotenone and
paraquat. Furthermore, we observed similar NF-kB activation with these
mitochondrial inhibitors. These results, together with inhibition of
laser induced NF-kB activation by antioxidants, suggests that ROS play
an important role in the laser induced NF-kB signaling pathways.
However, LLLT, unlike mitochondrial inhibitors, induced increased
cellular ATP levels, which indicates that LLLT also upregulates
We conclude that LLLT not only enhances mitochondrial
respiration, but also activates the redox-sensitive NFkB signaling via
generation of ROS. Expression of anti-apoptosis and pro-survival genes
responsive to NFkB could explain many clinical effects of LLLT.
FUll text- nice intro and review by Harvard prof
J Transl Med. 2010; 8: 16.
Lasers, stem cells, and COPD
Feng Lin,#1 Steven F Josephs,#1 Doru T Alexandrescu,#2
Famela Ramos,1 Vladimir Bogin,3 Vincent Gammill,4 Constantin A Dasanu,5
Rosalia De Necochea-Campion,6 Amit N Patel,7 Ewa Carrier,6 and David R
The medical use of low level laser (LLL) irradiation has
been occurring for decades, primarily in the area of tissue healing and
inflammatory conditions. Despite little mechanistic knowledge, the
concept of a non-invasive, non-thermal intervention that has the
potential to modulate regenerative processes is worthy of attention when
searching for novel methods of augmenting stem cell-based therapies.
Here we discuss the use of LLL irradiation as a "photoceutical" for
enhancing production of stem cell growth/chemoattractant factors,
stimulation of angiogenesis, and directly augmenting proliferation of
stem cells. The combination of LLL together with allogeneic and
autologous stem cells, as well as post-mobilization directing of stem
cells will be discussed.
"A pubmed search for "low level laser therapy" yields more
than 1700 results, yet before stumbling across this concept, none of us,
or our advisors, have ever heard of this area of medicine."
THE BIOLOGY OF NUCLEAR FACTOR KAPPA BETA (NFkB IN HEALTH AND PATHOLOGY by Carlos Kusano Bucalen Ferrari,
Biomedical Research Group, Institute of Biological and
Health Sciences (ICBS), “Campus Universitário do
Araguaia”, “Universidade Federal de Mato Grosso”
(UFMT), Barra do Garças, MT, Brazil.
J Mol Med (Berl). 2004 Jul;82(7):434-48. Epub 2004 Jun 3.
Nuclear factor-kappaB: its role in health and disease.
Kumar A, Takada Y, Boriek AM, Aggarwal BB.
Department of Medicine, Baylor College of Medicine, Houston,
TX 77030, USA. firstname.lastname@example.org
Nuclear factor-kappaB (NF-kappa is a major transcription
factor that plays an essential role in several aspects of human health
including the development of innate and adaptive immunity. The
dysregulation of NF-kappaB is associated with many disease states such
as AIDS, atherosclerosis, asthma, arthritis, cancer, diabetes,
inflammatory bowel disease, muscular dystrophy, stroke, and viral
infections. Recent evidence also suggests that the dysfunction of
NF-kappaB is a major mediator of some human genetic disorders.
Appropriate regulation and control of NF-kappaB activity, which can be
achieved by gene modification or pharmacological strategies, would
provide a potential approach for the management of NF-kappaB related
human diseases. This review summarizes the current knowledge of the
physiological and pathophysiological functions of NF-kappaB and its
possible role as a target of therapeutic intervention
“Use Mode 1 to re-energize muscle, ligament and tendon
cells for healing wounds and injuries or for reducing pain and
Mode 1 also benefits tendonitis, arthritis, burns, sprains,
cuts, bruises, muscle pulls, sore throat, and any pain or inflammation.”
• “Use Mode 2 to re-energize brain and heart cells and to
normalize brain neuropeptides and heart cell energy.”
• “Use Mode 3 as a multi-organ cell re-energizer that cycles
through 29 different frequencies proven effective and beneficial for
healing, and to benefit inflammation or disorders of all
internal, and for the treatment of any unknown condition.”
[Note: The proprioceptive points are
(1) just in front of the ear over the TMJ,
(2) under the angle of the jaw,
(3) two inches below the collar bone, and
(4) one inch up from the rounded angle of the shoulder blade
Evaluation of mitochondrial respiratory chain activity in muscle
healing by low-level laser therapy
Paulo C.L. Silveira a,*, Luciano Acordi da Silva a, Daiane B. Fraga b, Tiago P. Freitas b,
Emilio L. Streck b, Ricardo Pinho a
Background: Recent studies demonstrate that low-level laser therapy (LLLT) modulates many biochemical
processes, especially the decrease of muscle injures, the increase in mitochondrial respiration and ATP
synthesis for accelerating the healing process.
Objective: In this work, we evaluated mitochondrial respiratory chain complexes I, II, III and IV and succinate
dehydrogenase activities after traumatic muscular injury.
Methods: Male Wistar rats were randomly divided into three groups (n = 6): sham (uninjured muscle),
muscle injury without treatment, muscle injury with LLLT (AsGa) 5 J/cm2. Gastrocnemius injury was
induced by a single blunt-impact trauma. LLLT was used 2, 12, 24, 48, 72, 96, and 120 hours after muscle-
Results: Our results showed that the activities of complex II and succinate dehydrogenase after 5 days of
muscular lesion were significantly increased when compared to the control group. Moreover, our results
showed that LLLT significantly increased the activities of complexes I, II, III, IV and succinate dehydrogenase,
when compared to the group of injured muscle without treatment.
Conclusion: These results suggest that the treatment with low-level laser may induce an increase in ATP
synthesis, and that this may accelerate the muscle healing process.
Biomedical Optics & Medical Imaging
Low-level laser therapy: an emerging clinical paradigm
Ying-Ying Huang, Michael Hamblin, and Aaron C.-H. Chen
9 July 2009, SPIE Newsroom. DOI: 10.1117/2.1200906.1669
Improved understanding of the fundamental cellular and
molecular mechanisms is broadening the technique's mainstream use for
9 July 2009, SPIE Newsroom. DOI: 10.1117/2.1200906.1669
Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy
Patricia A Trimmer1*, Kathleen M Schwartz1, M Kathleen Borland1, Luis De Taboada2, Jackson Streeter2 and Uri Oron3
The NeuroThera® Laser System is under development for the
treatment of ischemic stroke and is not approved for sale or
distribution in the United States or internationally.
The NeuroThera® Laser System is an investigational device
that seeks to improve neurological outcomes via noninvasive delivery of
near-infrared (NIR) laser energy called Transcranial Laser Therapy (TLT)
into the brain. The system consists of a moveable console, a fiber
optic cable, and a handpiece. A trained clinician uses the handpiece to
direct the TLT to twenty predetermined treatment sites on the patient’s
scalp. The total procedure time is approximately 2-3 hours.
The Company believes that the NeuroThera® Laser System may
offer a compelling option for the treatment of acute ischemic stroke up
to twenty-four hours following onset of stroke symptoms.
Helium-neon laser irradiation stimulates cell proliferation through photostimulatory effects in mitochondria.
Hu WP, Wang JJ, Yu CL, Lan CC, Chen GS, Yu HS.
Faculty of Biotechnology and Graduate Institute of Medicine,
College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Previous reports have shown that cellular functions could be
influenced by visual light (400-700 nm). Recent evidence indicates that
cellular proliferation could be triggered by the interaction of a
helium-neon laser (He-Ne laser, 632.8 nm) with the mitochondrial
photoacceptor-cytochrome c oxidase.
Our previous studies
demonstrated that He-Ne irradiation induced an increase in cell
proliferation, but not migration, in the melanoma cell line A2058 cell.
The aim of this study was to investigate the underlying mechanisms
involved in photostimulatory effects induced by an He-Ne laser. Using
the A2058 cell as a model for cell proliferation, the photobiologic
effects induced by an He-Ne laser were studied. He-Ne irradiation
immediately induced an increase in mitochondrial membrane potential
(delta psi(mt)), ATP, and cAMP via enhanced cytochrome c oxidase
activity and promoted phosphorylation of Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) expressions.
He-Ne irradiation-induced A2058 cell proliferation was significantly
abrogated by the addition of delta psi(mt) and JNK inhibitors. Moreover,
treatment with an He-Ne laser resulted in delayed effects on IL-8 and
transforming growth factor-beta1 release from A2058 cells.
results suggest that He-Ne irradiation elicits photostimulatory effects
in mitochondria processes, which involve JNK/AP-1 activation and
enhanced growth factor release, and ultimately lead to A2058 cell
Dear Dr. Lytle:
During an inspection of your firm located in Rapid City,
South Dakota, on May 25 - 27, 2010, an investigator from the United
States Food and Drug Administration (FDA) learned that your firms 2035,
Inc. and QLaser Healing Light LP are marketing the Q10 Laser and 808
Enhancer Probe in the United States without marketing clearance or
approval, in violation of the Federal Food, Drug, and Cosmetic Act (the
Q1000 Laser and 660 Enhancer Probe
A review of our records indicates that we cleared a
premarket notification (510(k)) for the Q1000 Laser and 660 Enhancer
Probe (QLaser System), K080513, with an intended use “for providing
temporary relief of pain associated with osteoarthritis of the hand,
which has been diagnosed by a physician or other licensed medical
Trade/Device Name: QLaser System
Regulation Number: 21 CFR 890.5500
Regulation Name: Infrared lamp
Regulatory Class: II
Product Code: NHN
Dated: January 9, 2009
Received: January 12, 2009
RianCorp has completed the only randomised double blind
clinical trial testing the effects of LLLT on lymphoedema/lymphedema in
the world.7 Fleet St, Richmond, South Australia 5033
The LTU-904 models are infra-red lasers operating at a
wavelength of 904 nanometers. This invisible wavelength penetrates
deeply into tissue (much deeper than the often used red laser operating
in the visible red region).
RIFKIN MEDICAL PRODUCTS,LLC call 203-758-6569
The LTU-904 laser is only ONLY lymphoedema treatment that
has been trialled in a randomised double blind study. The laser works
very effectively in about 30% of patients and with some effect in about
50% of patients.
Absorption measurements of a cell monolayer relevant to phototherapy Reduction of cytochrome c oxidase under near
Tiina I. Karu a,*, Lydmila V. Pyatibrat a, Sergei F. Kolyakov b, Natalya I. Afanasyeva c
Journal of Photochemistry and Photobiology B: Biology 81 (2005) 98–106
a Institute of Laser and Information Technologies of Russian Academy of Sciences, Troitsk, Pionerskaya Street 2,
Moscow Region 142190, Russian Federation
b Institute of Spectroscopy of Russian Academy of Sciences, Troitsk, Moscow Region 142190, Russian Federation
c Spectrooptical Sensing Inc., Portland, OR 97205, USA
Received 26 April 2005; accepted 20 July 2005
Phototherapy uses monochromatic light in the optical
region of 600–1000 nm to treat in a non-destructive and non-thermal
various soft-tissue and neurological conditions. This kind
of treatment is based on the ability of light red-to-near IR to alter
cellular metabolism as a result of its being absorbed by cytochrome c oxidase. To further investigate the involvement of cytochrome
c oxidase as a photoacceptor in the alteration of the cellular metabolism,
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