Near-infrared light as a possible treatment option for Parkinson's disease and laser eye injury

DeSmet, Kristina; Buchmann, Ellen; Henry, Michele M.; Wong‐Riley, Margaret T.T.; Eells, Janis T.; VerHoeve, J. A.; Whelan, Harry T.

doi:10.1117/12.803964

Cited by 9 publications

(13 citation statements)

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“…Near infrared light (NIr; λ=600-1070nm) treatment is emerging as an effective neuroprotective therapy, one that is capable of limiting cell death in Parkinson's disease and other neurological conditions [5][6][7][8][9][10][11]. The bulk of evidence for neuroprotection is, however, very much at the basic science, proof-of-concept stage; to date, there are no major clinical studies reporting on neuroprotection in parkinsonian patients [11].…”

Section: The Effect Of Different Doses Of Near Infrared Light On Dopamentioning

confidence: 99%

The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

Massri

Johnstone

Peoples

et al. 2015

International Journal of Neuroscience

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We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice received MPTP injections (50 mg/kg) and 2 J/cm2 NIr dose with either 2 d or 7 d survival period. In another series, with a longer 14 d survival period, mice had a stronger MPTP regime (100 mg/kg) and either 2 J/cm2 or 4 J/cm2 NIr dose. Brains were processed for routine immunohistochemistry and cell counts were made using stereology. Our findings were that in the 2 d series, no change in SNc TH+ cell number was evident after any treatment. In the 7 d series however, MPTP insult resulted in ∼45% reduction in TH+ cell number; after NIr (2 J/cm2) treatment, many cells were protected from the toxic insult. In the 14 d series, MPTP induced a similar reduction in TH+ cell number. NIr mitigated the loss of TH+ cells, but only at the higher dose of 4 J/cm2; the lower dose of 2 J/cm2 had no neuroprotective effect in this series. The higher dose of NIr, unlike the lower dose, also mitigated the MPTP- induced increase in CPu astrocytes after 14 d; these changes were independent of TH+ terminal density, of which, did not vary across the different experimental groups. In summary, we showed that neuroprotection by NIr irradiation in MPTP-treated mice was dose-dependent; with increasing MPTP toxicity, higher doses of NIr were required to protect cells and reduce astrogliosis.

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Section: The Effect Of Different Doses Of Near Infrared Light On Dopamentioning

confidence: 99%

The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

Massri

Johnstone

Peoples

et al. 2015

International Journal of Neuroscience

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“…Recently, it has been shown that near‐infrared light (NIr) offers neuroprotection for various degenerative conditions, including PD . NIr treatment has been reported to reduce cell death, increase adenosine triphosphate (ATP) content, and decrease levels of oxidative stress among cultured cells after exposure to parkinsonian toxins .…”

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confidence: 99%

Near‐infrared light is neuroprotective in a monkey model of Parkinson disease

Darlot

Moro

Massri

et al. 2015

Annals of Neurology

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Objective: To examine whether near-infrared light (NIr) treatment reduces clinical signs and/or offers neuroprotection in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson disease. Methods: We implanted an optical fiber device that delivered NIr (670nm) to the midbrain of macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.5-2.1mg/kg) were made over a 5-to 7-day period, during which time the NIr device was turned on. This was then followed by a 3-week survival period. Monkeys were evaluated clinically (eg, posture, bradykinesia) and behaviorally (open field test), and their brains were processed for immunohistochemistry and stereology. Results: All monkeys in the MPTP group developed severe clinical and behavioral impairment (mean clinical scores 5 21-34; n 5 11). By contrast, the MPTP-NIr group developed much less clinical and behavioral impairment (n 5 9); some monkeys developed moderate clinical signs (mean scores 5 11-15; n 5 3), whereas the majority-quite remarkably-developed few clinical signs (mean scores 5 1-6; n 5 6). The monkeys that developed moderate clinical signs had hematic fluid in their optical fibers at postmortem, presumably limiting NIr exposure and overall clinical improvement. NIr was not toxic to brain tissue and offered neuroprotection to dopaminergic cells and their terminations against MPTP insult, particularly in animals that developed few clinical signs. Interpretation: Our findings indicate NIr to be an effective therapeutic agent in a primate model of the disease and create the template for translation into clinical trials.

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“…Hence, they assumed that the melanin in the fur absorbed most of the light before it reached the brain. 79 However, unlike the Moro et al study, DeSmet et al, 86 and Whelan et al, 52 reported improvements in mobility and velocity of movement in MPTP-treated pigmented mice (C57BL/6) after light treatment. One possible explanation for the differences in these studies is the use of a greater total light energy in the DeSmet et al and Whelan et al studies (8 and 30 joules/cm 2 , respectively) relative to the Moro study (2 joules/cm 2 ).…”

Section: Behavioral Improvementsmentioning

confidence: 94%

“…The restoration of functional activity in the basal ganglia by the surviving dopaminergic neurons manifests in 52,86,79 It also delays disease progression and reduces the severity of the disease phenotype in transgenic mice expressing the A53T human alpha-synuclein mutation. 87 In the MPTP-treated cases, the beneficial effects of light therapy are not immediate, being seen only after several doses of light over a period of 2-3 days.…”

Section: Behavioral Improvementsmentioning

confidence: 98%

The potential of light therapy in Parkinson's disease

Johnstone¹,

Coleman²,

Moro³

et al. 2014

CPT

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Parkinson's disease is a movement disorder with cardinal signs of resting tremor, akinesia, and rigidity. These manifest after a progressive death of many dopaminergic neurons of the midbrain. Unfortunately, the progression of this neuronal death has proved difficult to slow and impossible to reverse despite an intense search for the specific causes and for treatments that address the causes. There is a corresponding need to develop approaches that regulate the self-repair mechanisms of neurons, independent of the specific causes of the damage that leads to their death. Red to infrared light therapy (λ=600-1,070 nm) is emerging as an effective, repair-oriented therapy that is capable of stabilizing dying neurons. Initially a space-age anecdote, light therapy has become a treatment for tissue stressed by the known causes of age-related diseases: hypoxia, toxic environments, and mitochondrial dysfunction. Here we focus on several issues relating to the use of light therapy for Parkinson's disease: 1) What is the evidence that it is neuroprotective? We consider the basic science and clinical evidence; 2) What are the mechanisms of neuroprotection? We suggest a primary mechanism acting directly on the neuron's mitochondria (direct effect) as well as a secondary, supportive mechanism acting indirectly through systemic systems (indirect effect); 3) Could this be effective in humans? We discuss the pros and cons of this treatment in humans, including the development of a new surgical method of delivery; and 4) What are the advantages of using light therapy? We explore the features that make this therapy a promising potential treatment. In summary, early evidence indicates that light regulates specific neuronal functions and is neuroprotective in animal models of Parkinson's disease. The stage is set for detailed and rigorous explorations into its use on Parkinson's disease patients, in particular, whether light slows the disease progression rather than simply mitigating signs.

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Near-infrared light as a possible treatment option for Parkinson's disease and laser eye injury

Cited by 9 publications

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The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

Near‐infrared light is neuroprotective in a monkey model of Parkinson disease

The potential of light therapy in Parkinson's disease

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Near-infrared light as a possible treatment option for Parkinson's disease and laser eye injury

Cited by 9 publications

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The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

Near‐infrared light is neuroprotective in a monkey model of Parkinson disease

The potential of light therapy in Parkinson&#39;s disease

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The potential of light therapy in Parkinson's disease