No evidence for toxicity after long-term photobiomodulation in normal non-human primates
- 228 Downloads
In this study, we explored the effects of a longer term application, up to 12 weeks, of photobiomodulation in normal, naïve macaque monkeys. Monkeys (n = 5) were implanted intracranially with an optical fibre device delivering photobiomodulation (red light, 670 nm) to a midline midbrain region. Animals were then aldehyde-fixed and their brains were processed for immunohistochemistry. In general, our results showed that longer term intracranial application of photobiomodulation had no adverse effects on the surrounding brain parenchyma or on the nearby dopaminergic cell system. We found no evidence for photobiomodulation generating an inflammatory glial response or neuronal degeneration near the implant site; further, photobiomodulation did not induce an abnormal activation or mitochondrial stress in nearby cells, nor did it cause an abnormal arrangement of the surrounding vasculature (endothelial basement membrane). Finally, because of our interest in Parkinson’s disease, we noted that photobiomodulation had no impact on the number of midbrain dopaminergic cells and the density of their terminations in the striatum. In summary, we found no histological basis for any major biosafety concerns associated with photobiomodulation delivered by our intracranial approach and our findings set a key template for progress onto clinical trial on patients with Parkinson’s disease.
KeywordsTyrosine hydroxylase Substantia nigra Striatum Macaque monkeys Behaviour 670 nm
We are forever grateful to Michael J. Fox Foundation, Credit Agricole Sud Rhones Alpes, Fondation Philanthropique Edmond J Safra, Fondation Avenir, France Parkinson and the French National Research Agency (ANR Carnot Institute), Tenix corp and Salteri family and our industry partners for funding this work. We thank Darryl Cameron, Sharon Spana, Guillaume Barboux, Clément Perrin, Cyril Zenga and Mylène D’Orchymont for excellent technical assistance. The authors declare no conflict of interest with this work. All authors contributed to the experiments and analysis of the results and CM, ALB and JM to the writing of the manuscript.
- Kordorwer J, Muller S, Marck K et al (2015) Photobiomodulation in aged non-human primates. Society for Neuroscience, Chicago. Poster 217.20/C80Google Scholar
- Liang HL, Whelan HT, Eells JT, Wong-Riley MTT (2008) Near-infrared light via light-emitting diode treatment is therapeutic against rotenone- and 1-methyl-4-phenylpyridinium ion-induced neurotoxicity. Neuroscience 153:963–974. doi: 10.1016/j.neuroscience.2008.03.042 CrossRefPubMedPubMedCentralGoogle Scholar
- Merry G, Dotson R, Devenyi R et al (2012) Photobiomodulation as a new treatment for dry age related macular degeneration. Results from the Toronto and Oak Ridge photobiomodulation study in AMD (TORPA). Invest Ophthalmol Vis Sci 53:2049Google Scholar
- Paxinos G, Huang X, Toga A (1998) The Rhesus monkey brain in stereotaxic coordinates. Academic Press, USAGoogle Scholar
- Reinhart F, El Massri N, Darlot F et al (2015) Evidence for improved behaviour and neuroprotection after intracranial application of near infrared light in a hemi-parkinsonian rat model. J Neurosurg 27:1–13Google Scholar
- Schiffer F, Johnston AL, Ravichandran C et al (2009) Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct 5:46. doi: 10.1186/1744-9081-5-46 CrossRefPubMedPubMedCentralGoogle Scholar