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10.1117/2.1201504.005900
Light therapy to treat
autoimmune disease
Jeri-Anne Lyons
Experiments in an animal model of multiple sclerosis demonstrate
the therapeutic potential of 670nm light treatment.
Inflammation is a double-edged sword. Controlled inflamma-
tion is necessary for maintaining physiologic homeostasis and
is critical to the natural healing process. However, unchecked
inflammation leads to the accumulation of oxidative and
nitrosative stress in the body, compromising the structure and
function of proteins, lipids, and nucleic acids. By modifying
these important macromolecules, inflammation contributes
to the natural aging process and a wide variety of disease
pathologies, including obesity, diabetes, autoimmunity, and
neurodegeneration (see Figure 1).
Multiple sclerosis (MS) is a chronic, neurodegenerative
autoimmune disease of the central nervous system (CNS), which
is mediated by myelin-reactive lymphocytes, leading to chronic
inflammation in the CNS. Recent data suggest that chronic MS
develops in two parts: an initial autoimmune stage, and a sub-
sequent neurodegenerative episode characterized by ongoing
nitrosative and oxidative stress1–3. Current therapies target the
immune response and slow disease progression, but they do
not prevent it, probably because of a lack of protection against
the ongoing neurodegeneration. Effective treatment of MS
relies on the development of neuroprotective strategies that tar-
get the nitrosative and oxidative stress responsible for chronic
disease.
Photobiomodulation (PBM) therapy, using far red/near IR
(FR/NIR) laser light (630–1000nm), offers promise as an effective
treatment for chronic inflammation and neurodegeneration. One
hypothesis to explain the PBM mechanism describes mitochon-
drial cytochrome c oxidase (CcO) as a photoreceptor for FR/NIR
light. Absorption of the light by CcO leads to restoration of
mitochondrial induction of gene transcription. The outcome
of photobiomodulation is the down-regulation of pro-inflammatory
processes, up-regulation of anti-inflammatory mechanisms, and
restoration of physiology.4The autoimmune and neurode-
generative processes culminating in pathogenesis led us to
Figure 1. Consequences of inflammation.
Table 1. Clinical grading of the severity of experimental autoimmune
encephalomyelitis (EAE).
Grade Clinical Signs
0 Healthy; none
1 Loss of tail tone
2 Hind limb weakness
3 Single hind limb paralysis
4 Double hind limb paralysis
5 Front limb weakness/paralysis
hypothesize that photobiomodulation may be an effective
treatment strategy for MS.
To investigate this idea, we considered experimental autoim-
mune encephalomyelitis (EAE), the primary animal model for
the study of MS. We can induce EAE in susceptible species
and strains by immunization with proteins found in the myelin
sheath surrounding axons of the CNS neurons. For example,
immunization of C57BL/6 mice with myelin oligodendrocyte
glycoprotein (MOG) leads to a chronic disease characterized
by ascending paralysis reminiscent of chronic or late stage MS
(see Figure 2)1. Typically, we grade disease on a scale of 0–5,
where 0 is indicative of a healthy mouse and 5 of severe disease
(See Table 1 )5.
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10.1117/2.1201504.005900 Page 2/2
We used the EAE model to investigate the therapeutic
potential of photobiomodulation for the treatment of MS. We
immunized C57BL/6 mice with MOG, and when clinical
signs became apparent, we assigned the mice to two groups:
one receiving light treatment, and the other receiving a sham.
Those receiving light treatment received one daily exposure to
670nm light delivered with gallium/arsenic/aluminum LEDs
at a dose of 4J/cm2for seven days, followed by seven days of
no light treatment, and a subsequent seven-day treatment
period. We assessed for clinical disease for seven days following
the last light treatment. We exposed the sham treatment group
to restraint stress only, placing it in the polypropylene treatment
chamber but not exposing it to light. Assessment of clinical
severity revealed that treatment with 670nm light ameliorated
the course of disease compared to sham-treated animals5(see
Figure 2). We associated the improvement of clinical signs with
the down-regulation of pro-inflammatory mediators and the
up-regulation of anti-inflammatory mediators. Furthermore,
immunohistochemical analysis revealed less cell death
(apoptosis) in mice receiving 670nm light treatment compared
to sham-treated animals throughout the course of disease.6
MS is a dynamic and unpredictable condition, with patients
experiencing periods of relapse and remission as the opposing
pro- and anti-inflammatory mechanisms mediate disease
activity. As experiments progress towards clinical studies,
one important factor to consider is the selection of wavelength.
The 670nm light used in animal studies may be ineffective in
patients due to a lack of penetration to the CNS. Early animal
Figure 2. Amelioration of clinical disease severity in an animal model
of chronic multiple sclerosis. We immunized mice with myelin oligo-
dendrocyte glycoprotein, amino acids 35-55, to induce EAE. We treated
the mice for seven days beginning on the day of onset of clinical signs,
followed by seven days of no light treatment, and a subsequent seven-
day treatment period.5
studies with 830nm light, which does penetrate to the human
CNS, demonstrated an exacerbating effect on early clinical signs
and less effective amelioration during the chronic phase of
disease. With optimization of treatment parameters, our data
indicate that photobiomodulation may be an effective treatment
that not only targets the immune response, but also offers the
neuroprotection lacking with current treatment strategies. The
dual action of photobiomodulation may thus provide an
effective treatment for MS, and our future work will focus on
realizing that aim.
Author Information
Jeri-Anne Lyons
University of Wisconsin-Milwaukee
Milwaukee, WI
Jeri-Anne Lyons is an associate professor in the Biomedical
Sciences department.
References
1. L. Steinman, Immunology of Relapse and Remission in Multiple Sclerosis,Annu. Rev.
Immunol. 32, pp. 257–281, 2014. doi:10.1146/annurev-immunol-032713-120227
2. R. Dutta, J. McDonough, X. Yin, J. Peterson, A. Chang, T. Torres, T. Gudz, et al.,
Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients,
Ann. Neurol. 59 (3), pp. 478–489, 2006. doi:10.1002/ana.20736
3. R. Dutta and B. D. Trapp, Pathogenesis of axonal and neuronal damage in multiple
sclerosis,Neurol. 22 (22, suppl 3), pp. S22–31, S43–54, 2007.
4. H. Chung, T. Dai, S. K. Sharma, Y. Y. Huang, J. D. Carroll, and M. R. Hamblin, The
nuts and bolts of low-level laser (light) therapy,Ann. Biomed. Eng. 40 (2), pp. 516–33,
2012. doi:10.1007/s10439-011-0454-7
5. K. A. Muili, S. Gopalakrishnan, S. L. Meyer, J. T. Eells, and J.-A. Lyons,
Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by
photobiomodulation induced by 670nm light,PLoS ONE 7 (1), p. e30655, 2012.
doi:10.1371/journal.pone.0030655
6. K. A. Muili, S. Gopalakrishnan, J. T. Eells, and J. A. Lyons, Photobiomodula-
tion induced by 670nm light ameliorates MOG35-55 induced EAE in female C57BL/6
mice: a role for remediation of nitrosative stress,PLoS ONE 8 (6), p. e67358, 2013.
doi:10.1371/journal.pone.0067358
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2015 SPIE