Clinical Research
ALL RESEARCH BY DRS. WHELAN, WONG-RILEY
AND EELLS AT THE MEDICAL COLLEGE OF
WISCONSIN HAS BEEN COMPLETED
WITH QUANTUM DEVICES LED ARRAYS [Researcher
Bios]
Facial Rejuvenation in the Triangle of ROS (2009)
Abstract: Recently, we introduced into the conventional
catalogue of biological aging a new determinant: ordered interfacial water
layers. The discovery of their tunability with skin-tolerated levels of 670
nm light inspired a model, which suggested that the light, by interaction
with ordered interfacial water layers in the extracellular matrix, would
reverse elastin degeneration. We validated the model in a 10 month self-experiment
and arrived at an effective facial rejuvenation program. Importantly, during
the experimental phase we avoided extreme oxidative stressors, in particular
exposure to extensive ultraviolet and infrared radiation as well as air pollution.
Here we report on the adaptation of our model to the extreme oxidative stress
levels prevalent in numerous polluted megacities. The results of the extension
comprise a new understanding of the protective function of the skin acid
mantle, new predictive insight into effects of reactive oxygen species (ROS)
on interfacial water layers, and their implication in processes of biological
aging, including depletion of follicular stem cell reservoirs and telomere
shortening, and led to the design of an accelerated skin rejuvenation method.
Effects of Low-Level Light Therapy
on Hepatic Antioxidant Defense in Acute and Chronic Diabetic Rats (2009)
Abstract: Diabetes causes oxidative stress in the liver and other tissues
prone to complications. Photobiomodulation by near infrared light (670 nm)
has been shown to accelerate diabetic wound healing, improve recovery from
oxidative injury in the kidney, and attenuate degeneration in retina and
optic nerve. The present study tested the hypothesis that 670 nm photobiomodulation,
a low-level light therapy, would attenuate oxidative stress and enhance the
antioxidant protection system in the liver of a model of type I diabetes.
MaleWistar rats were made diabetic with streptozotocin (50 mg/kg, ip) then
exposed to 670 nm light (9 J/cm2) once per day for 18 days (acute) or 14
weeks (chronic). Livers were harvested, flash frozen, and then assayed for
markers of oxidative stress. Light treatment was ineffective as an antioxidant
therapy in chronic diabetes, but light treatment for 18 days in acutely diabetic
rats resulted in the normalization of hepatic glutathione reductase and superoxide
dismutase activities and a significant increase in glutathione peroxidase
and glutathione-S transferase activities. The results of this study suggest
that 670 nm photobiomodulationmay reduce, at least in part, acute hepatic
oxidative stress by enhancing the antioxidant defense system in the diabetic
ratmodel.
Abstract: Photobiomodulation with near infrared light (NIR) provides cellular protection in various disease models. Previously, infrared light emitted by a low-energy laser has been shown to significantly improve recovery from ischemic injury of the canine heart. The goal of this investigation was to test the hypothesis that NIR (670 nm) from light emitting diodes produces cellular protection against hypoxia and reoxygenation-induced cardiomyocyte injury. Additionally, nitric oxide (NO) was investigated as a potential cellular mediator of NIR. Our results demonstrate that exposure to NIR at the time of reoxygenation protects neonatal rat cardiomyocytes and HL-1 cells from injury, as assessed by lactate dehydrogenase release and MTT assay. Similarly, indices of apoptosis, including caspase 3 activity, annexin binding and the release of cytochrome c from mitochondria into the cytosol, were decreased after NIR treatment. NIR increased NO in cardiomyocytes, and the protective effect of NIR was completely reversed by the NO scavengers carboxy- PTIO and oxyhemoglobin, but only partially blocked by the NO synthase (NOS) inhibitor L-NMMA. Mitochondrial metabolism, measured by ATP synthase activity, was increased by NIR, and NO-induced inhibition of oxygen consumption with substrates for complex I or complex IV was reversed by exposure to NIR. Taken together these data provide evidence for protection against hypoxia and reoxygenation injury in cardiomyocytes by NIR in a manner that is dependent upon NO derived from NOS and non-NOS sources.
Pretreatment with near-infrared light via light-emitting
diode provides added benefit against rotenone- and MPP+-induced neurotoxicity (2008)
Abstract: Parkinson's disease (PD)
is a movement disorder caused by the loss of dopaminergic neurons in the
substantia nigra pars compacta, leading to nigrostriatal degeneration. The
inhibition of mitochondrial respiratory chain complex I and oxidative stress-induced
damage have been implicated in the pathogenesis of PD. The present study
used these specific mitochondrial complex I inhibitors (rotenone and 1-methyl-4-phenylpyridinium
or MPP+) on striatal and cortical neurons in culture. The goal was to test
our hypothesis that pretreatment with near-infrared light (NIR) via light-emitting
diode (LED) had a greater beneficial effect on primary neurons grown in media
with rotenone or MPP+ than those with or without LED treatment during exposure
to poisons. Striatal and visual cortical neurons from newborn rats were cultured
in a media with or without 200 nM of rotenone or 250 μMof MPP+ for 48 h.
They were treated with NIR-LED twice a day before, during, and both before
and during the exposure to the poison. Results indicate that pretreatment
with NIR-LED significantly suppressed rotenone- or MPP+-induced apoptosis
in both striatal and cortical neurons (P<0.001), and that pretreatment
plus LED treatment during neurotoxin exposure was significantly better than
LED treatment alone during exposure to neurotoxins. In addition, MPP+ induced
a decrease in neuronal ATP levels (to 48% of control level) that was reversed
significantly to 70% of control by NIR-LED pretreatment. These data suggest
that LED pretreatment is an effective adjunct preventative therapy in rescuing
neurons from neurotoxins linked to PD.
Modulation of rat pituitary
growth hormone by 670 nm light (2008)
Abstract: In rat pituitary somatotrophs, cytochrome oxidase is co-packaged
with growth hormone (GH) in some 20 storage granules. Because this enzyme
is thought to be the molecular photoacceptor of red-near infrared 21 light,
and because exposure of diverse tissue systems to 670 nm visible light affects
their biological 22 responses (e.g., wound healing), we tested the idea that
exposure of rat pituitary cells, rat hemi-pituitary 23 glands and rat pituitary
homogenates to 670 nm light in vitro might alter GH storage and/or release.
In 24 this report we offer evidence to show that light treatment (670 nm,
80 s, intensity 50 mW/cm2, energy 25 density 4 J/cm2) up-regulates GH release,
in part by breakdown of intracellular, oligomeric GH as deter- 26 mined by
gel filtration chromatography.
NEAR-INFRARED LIGHT VIA LIGHT-EMITTING
DIODE TREATMENT IS THERAPEUTIC AGAINST ROTENONE- AND 1-METHYL-4- PHENYLPYRIDINIUM
ION-INDUCED NEUROTOXICITY (2008)
Abstract: Parkinson’s disease is
a common progressive neurodegenerative disorder characterized by the degeneration
of dopaminergic neurons in the substantia nigra pars compacta. Mitochondrial
dysfunction has been strongly implicated in the pathogenesis of Parkinson’s
disease. Thus, therapeutic approaches that improve mitochondrial function
may prove to be beneficial. Previously, we have documented that near-infrared
light via light-emitting diode (LED) treatment was therapeutic to neurons
functionally inactivated by tetrodotoxin, potassium cyanide (KCN), or methanol
intoxication, and LED pretreatment rescued neurons from KCNinduced apoptotic
cell death. The current study tested our hypothesis that LED treatment can
protect neurons from both rotenone- and MPP+-induced neurotoxicity. Primary
cultures of postnatal rat striatal and cortical neurons served as models,
and the optimal frequency of LED treatment per day was also determined. Results
indicated that LED treatments twice a day significantly increased cellular
adenosine triphosphate content, decreased the number of neurons undergoing
cell death, and significantly reduced the expressions of reactive oxygen
species and reactive nitrogen species in rotenone- or MPP+-exposed neurons
as compared with untreated ones. These results strongly suggest that LED
treatment may be therapeutic to neurons damaged by neurotoxins linked to
Parkinson’s disease by energizing the cells and increasing their viability.
Photobiomodulation for the Treatment
of Retinal Injury and Retinal Degenerative Diseases (2008)
Abstract: Retinal injury and retinal degenerative diseases are a leading
causes of visual impairment in the developed world. Mitochondrial dysfunction
and oxidative stress play key roles in the pathogenesis of retinal injury
and disease. The development and testing of strategies designed to improve
mitochondrial function and attenuate oxidative stress are essential for combating
retinal disease. One strategy involves the use of photobiomodulation. Photobiomodulation,
low-energy photon irradiation by light in the far-red to nearinfrared (NIR)
range using low energy lasers or light-emitting diode (LED) arrays, has been
applied clinically in the treatment soft tissue injuries and acceleration
of wound healing for more than 30 years. The therapeutic effects of photobiomodulation
have been hypothesized to be mediated by intracellular signaling mechanisms
triggered by the interaction of far-red to NIR photons with the mitochondrial
photoacceptor molecule cytochrome oxidase which culminate in improved mitochondrial
energy metabolism, increased synthesis of cytoprotective factors and cell
survival.
PHOTOMODULATION OF CYTOCHROME OXIDASE (2006)
Objectives: Photobiomodulation by red to near infrared light is believed
to activate mitochondrial respiratory chain components promoting cytoprotecton.
Recent studies in our laboratory demonstrate that the action spectrum for
stimulation of cytochrome oxidase activity and cellular ATP parallels the
nearinfrared absorption spectrum of cytochome oxidase and that 660–680
nm irradiation upregulates cytochrome oxidase activity in cultured neurons.
Methanol intoxication injures the retina and optic nerve. Via formic acid,
a mitochondrial toxin of cytochrome oxidase. KCN (potassium cyanide) also
poisons cytochrome oxidase, and has been used to assess the efficacy of
660– 680 nm irradiation for mitochondrial neuroprotection.
Embryonic Growth and Hatching Implications
of Developmental 670-nm Phototherapy and Dioxin Co-exposure (2006)
Objective: We assessed the effect of 670-nm light therapy on growth and hatching
kinetics in chickens (Gallus gallus) exposed to dioxin. Background Data:
Photobiomodulation has been shown to stimulate signaling pathways resulting
in improved energy metabolism, antioxidant production, and cell survival.
In ovo treatment with 670-nm light-emitting diode (LED) arrays improves hatching
success and increases hatchling size in control chickens. Under conditions
where developmental dioxin exposure is above the lethality threshold (100
ppt), phototherapy attenuates dioxin-induced early embryonic death. We hypothesized
that 670-nm LED therapy would attenuate dioxin-induced developmental anomalies
and increase hatching success.
Stressed Cells Survive Better with Light (2002)
Abstract: Biostimulatory effects achieved in various biosystems irradiated
with light lead us to recommend photobiostimulation for the compensation
of external stress stimuli in tissue engineering, as well as in cellular
imaging. Bioengineered cell assemblies and tissues are exposed to extreme
environmental stress states during their transfer from artificial milieus
into the body and in the first phase of their implantation. Similarly,
cellular imaging via optical methods could represent a major stress impact
to the biosystems examined, in particular, in temporally extended investigations.
In both cases, an elevated and gradually proceeding environmental stress
would inhibit cellular functions and enhance cell death.
Nature Inspired Hay Fever Therapy
Abstract: The survival oriented adaptation of evolved biosystems to variations
in their environment is a selective optimization process. Recognizing the
optimised end product and its functionality is the classical arena of bionic
engineering. In a primordial world, however, the molecular organization
and functions of prebiotic systems were solely defined by formative processes
in their physical and chemical environment, for instance, the interplay
between interfacial water layers on surfaces and solar light. The formative
potential of the interplay between light (laser light) and interfacial
water layers on surfaces was recently exploited in the formation of supercubane
carbon nanocrystals. In evolved biosystems the formative potential of interfacial
water layers can still be activated by light. Here we report a case of
hay fever, which was successfully treated in the course of a facial rejuvenation
program starting in November 2007. Targeting primarily interfacial water
layers on elastin fibres in the wrinkled areas, we presumably also activated
mast cells in the nasal mucosa, reported to progressively decrease in the
nasal mucosa of the rabbit, when frequently irradiated. Hay fever is induced
by the release of mediators, especially histamine, a process associated
with the degranulation of mast cells. Decrease in mast cells numbers implies
a decrease in the release of histamine. To the best of our knowledge this
is the first report on the treatment of hay fever with visible light. This
approach was inspired by bionic thinking, and could help ameliorating the
condition of millions of people suffering from hay fever world wide.
From Microtornadoes to Facial Rejuvenation:
Implication of Interfacial Water Layers
Abstract: Crystalline interfacial water
layers have been observed at room temperature on both hydrophobic
and hydrophilic surfaces - in air and subaquatically. Their implication
in biology (and evolution) was postulated in a visionary paper
in 1971 by Szent Gyo¨ rgyi. Today, they are believed to play a
fundamental role in protein folding. A recent X-ray diffraction
study reports on their presence on crystals in contact with their
growth solution. Their subaquatic persistence on hydrophobic solids
was reported in 2007. Their relevance in nanoscale phenomena is
reflected by the multidisciplinary focus in their study. In the
course of a systematic exploration of interfacial water layers
on solids we discovered microtornadoes, found a complementary explanation
to the surface conductivity on hydrogenated diamond, and arrived
at a practical method to repair elastin degeneration using light.
The result was rejuvenated skin, reduced wrinkle levels, juvenile
complexion, and lasting resilience.
Effects of Continuous-Wave (670-nm) Red Light
on Wound Healing
Abstract: Recent work
suggests that injuries can heal faster if treated by lasers emitting
670-nm red light. LED lights emitting 670-nm light are now available.
This suggests that inexpensive and easyto- use 670-nm LED lights
might help accelerate cutaneous wound healing. The objective was
to evaluate the effect of 670-nm LED light on wound healing in SKH-1 hairless
mice.
Biostimulatory
Windows in Low-Intensity Laser Activation: Lasers, Scanners,
and NASA’s Light-Emitting Diode Array System
Abstract: The purpose of this study was to assess and to formulate
physically an irreducible set of irradiation parameters that could
be relevant in the achieving reproducible light-induced effects in
biological systems, both in vitro and in vivo.
Clinical
and Experimental Applications of NIR-LED Photobiomodulation
Abstract: This review
presents current research on the use of far-red to near-infrared
(NIR) light treatment in various in vitroand in vivomodels. Low-intensity
light therapy, commonly referred to as “photobiomodulation,” uses
light in the far-red to near-infrared region of the spectrum (630–1000
nm) and modulates numerous cellular functions. Positive effects
of NIR–light-emitting diode (LED) light treatment include acceleration
of wound healing, improved recovery from ischemic injury of the
heart, and attenuated degeneration of injured optic nerves by improving
mitochondrial energy metabolism and production.
DARPA
Soldier Self Care: Rapid Healing of Laser Eye Injuries
with Light Emitting Diode Technology
Abstract: 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 and attenuate degeneration in the injured optic nerve. At
the cellular level, photoirradiation at low fluences can generate
significant biological effects including cellular proliferation
and the release of growth factors from cells.
Effect
of NASA Light-Emitting Diode Irradiation on Molecular Changes
for Wound Healing in Diabetic Mice
Abstract: The purpose
of this study was to assess the changes in gene expression of near-infrared
light ther- apy in a modcl of impaired wound healing. Background
Data: Light-Emitting Diodes (LED), originally devel- nped fnr NASA
plant grrrwth experiments in space, show promise for delivering
light deep into tissues of the body to promote wound healing and
human tissue growth. In this paper we present the effects of LED
treat- ment on wounds in a genetically diabetic mouse model.
Effect
of NASA Light-Emitting Diode Irradiation on Wound Healing
Abstract: The purpose of this study was
to assess the effects of hyperbaric oxygen (HBO) and near-infrared
light therapy on wound healing. Background Data: Light-emitting
diodes (LED), originally developed for NASA plant growth experiments
in space show promise for delivering light deep into tissues of
the body to pro- mote wound healing and human tissue growth. In
this paper, we review and present our new data of LED treatment
on cells grown in culture, on ischemic and diabetic wounds in rat
models, and on acute and chronic wounds in humans.
Effects of 670-nm
Phototherapy on Development
Abstract: The
objective of the present study was to assess the survival and hatching
success of chickens (Gallus gallus) exposed in ovoto far-red (670-nm)
LED therapy. Background Data:Photobiomodulation by light in the
red to near-infrared range (630–1000 nm) using low-energy lasers
orlight-emitting diode (LED) arrays has been shown to accelerate
wound healing and improve recovery from ischemic injury.
Evaluation
of photodynamic therapy near functional brain tissue in
patients with recurrent brain tumors
Abstract: Photodynamic
therapy (PDT) involves the selective retention of a photosensitizer
that upon activation with light mediates tumor cell destruction
via the production of singlet oxygen. This study evaluates the
toxicity of PDT and a new light-delivery device based on light-emitting
diode (LED) technology in selected patients with brain tumors.
Innate
immunity for biodefense: A strategy whose time has come
Abstract: Defense against
biothreat agents requires a broad-spectrum approach. Modulation
of the innate immune system might fulfill this requirement. Hackett’s
previous review of innate immune activation as a broad-spectrum
biodefense strategy identified several unresolved questions. The
current article is a systematic approach to answering those questions
with the focused participation of research groups developing this
technology.
Light-emitting
diode treatment reverses the effect of TTX on cytochrome
oxidase in neurons
Abstract: Light close
to and in the near-infrared range has documented benefits for promoting
wound healing in human and animals. However, mechanisms of its
action on cells are poorly undersottd. We hypothesied that light
treatment with a light emitting diode array at 670nm (LED) is theraputic
in stimulating cellular events involving increases in ctochrome
oxidase activity.
Light-emitting
Diodes as a Light Source for Intraoperative Photodynamic
Therapy
Abstract: The development
of more cost-effective light sources for photodynamic therapy of
brain tumors would be of benefit for both research and clinical
applications. In this study, the u se of light-emitting diode arrays
for photodynamic therapy of brain tumors with Photofrin porfimer
sodium was investigated.
Medical
Applications of Space Light-Emitting Diode Technology -
Space Station and Beyond
Abstract: Space light-emitting
diode (LED) technology has provided medicine with a new tool capable
of delivering light deep of the body, at wavelengths which are
biologically optimal for cancer treatment and wound healing. This
LED technology has already flown on Space Shuttle missions. and
shows promise for wound healing applications of benefit to Space
Station astronauts.
Mitochondrial
signal transduction in accelerated wound and retinal healing
by near-infrared light therapy
Abstract: 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.
NASA
Light Emitting Diode Medical Applications From Deep Space
to Deep Sea
Abstract: LED-technology
developed for NASA plant growth experiments in space shows promise
for delivering light deep into tissues of the body to promote wound
healing and human tissue growth. We present the results of LED-treatment
of cells grown in culture and the effects of LEDs on patients’
chronic and acute wounds. LED-technology is also biologically optimal
for photodynamic therapy of cancer and we discuss our successes
using LEDs in conjunction with light-activated chemotherapeutic
drugs.
NASA
Light-Emitting Diode Medical Program - Progress in Space
Flight and Terrestrial Applications
Abstract: Studies on cells
exposed to microgravity and hypergravity indicate that human cells
need gravity to stimulate cell growth. As the gravitational force
increases or decreases, the cell function responds in a linear
fashion. This poses significant health risks for astronauts in
long termspace flight. LED-technology developed for NASA plant
growth experiments in space shows promise for delivering light
deep into tissues of the body to promote wound healing and human
tissue growth. This LED-technology is also biologically optomal
for photodynamic therapy of cancer.
NASA
Light-Emitting Diodes for the Prevention of Oral Mucositis
in Pediatric Bone Marrow Transplant Patients
Abstract: The purpose
of this study was to determine the effects of prophylactic near-infrared
light therapy from light-emitting diodes (LEDs) in pediatric bone
marrow transplant (BMT) recipients. Background Data: Oral mucositis
(OM) is a frequent side effect of chemotherapy that leads to increased
morbidity. Near- infrared light has been shown to produce biostimulatory
effects in tissues, and previous results using near- infrared lasers
have shown improvement in OM indices. However, LEDs may hold greater
potential for clinical applications.
Photobiomodulation
Directly Benefits Primary Neurons Functionally Inactivated
by Toxins
Abstract: Far red and
near infrared (NIR) light promotes wound healing, but the mechanism
is poorly understood. Our previous studies using 670 nm light-emitting
diode (LED) arrays suggest that cytochrome c oxidase, a pho- toacceptor
in the NIR range, plays an important role in therapeutic photobiomodulation.
If this is true, then an irreversible inhibitor of cytochrome c
oxidase, potas- sium cyanide (KCN), should compete with LED and
re- duce its beneficial effects. This hypothesis was tested on
primary cultured neurons.
Photobiomodulation
Partially Rescues Visual Cortical Neurons from Cyanide-induced
Apoptosis
Abstract: Near-infrared
light via light-emitting diode treatment has documented therapeutic
effects on neurons functionally inactivated by tetrodotoxin or
methanol intoxication. Light-emitting diode pretreatment also reduced
potassium cyanide-induced cell death, but the mode of death via
the apoptotic or necrotic pathway was unclear. The current study
tested our hypothesis that light-emitting diode rescues neurons
from apoptotic cell death.Possible mechanisms involve an acceleration
of electron transfer in the respiratory chain and activation of
photoacceptors, such as cytochrome oxidase, thus pointing to a
particular role for mitochondria.
Preliminary
Investigation into Light-Modulated Replication of Nanobacteria
and Heart Disease
Abstract: The purpose
of this preliminary study is to evaluate the effect of various
wavelengths of light on nanobacteria (NB). Background Data: NB
and mitochondria use light for biological processes. NB have been
described as multifunctional primordial nanovesicles with the potential
to utilize solar energy for replication. NB produce slime, a pro
cess common to living bacteria. Slime release is an evolutionary
important stress- dependent phenomenon increasing the survival
chance of individual bacteria in a colony. In the cardiovascu-
lar system, stress-induced bacterial colony formation may lead
to a deposition of plaque.
Therapeutic photobiomodulation for methanol-induced
retinal toxicity
Abstract: Methanol intoxication
produces toxic injury to the retina and optic nerve, resulting
in blindness. The toxic metabolite in methanol intoxication is
formic acid, a mitochondrial toxin known to inhibit the essential
mitochondrial enzyme, cytochrome oxidase. Photobiomodulation by
red to near-IR radiation has been demonstrated to enhance mitochondrial
activity and promote cell survival in vitro by stimulation of cytochrome
oxidase activity.
