Near-infrared Light Treatment Research Articles

The effect of near-infrared low-level light on the in vitro quality of platelets during storage.

Near-infrared (NIR) light has been successfully applied to improve the quality of mouse platelets during storage. Because it is suspected that the mitochondria contain the primary photon acceptor, we hypothesized that human platelets for transfusion may be affected similarly and could benefit from NIR light treatment. The optimal light dose was determined using portions of platelet concentrates (PCs) in PAS-E. A pool-and-split design was used to prepare PCs in PAS-E or plasma (n = 6). On day 1, one unit of both pairs was illuminated with 830 nm light (light-emitting diodes, 15 J/cm2). PCs were stored at 22°C and sampled regularly for analysis. Data were compared with their corresponding controls with a paired two-sided t-test. Illuminated platelets in PAS-E were less activated with significantly lower CD62P expression (day 8: 10.8 ± 1.8 vs. 12.2 ± 2.6, p < 0.05) and lower Annexin A5 binding (day 8: 11.8 ± 1.9 vs. 13.1 ± 2.4, ns). They produced significantly less lactate resulting in a higher pH (days 6-10). ATP content and mitochondrial membrane potential were not affected. Although these trends were also observed for PCs in plasma, the differences did not reach statistical significance as compared with the control group. Our study demonstrates that the glycolysis rate of human platelets can be modulated through the use of NIR, possibly through mitochondrial aerobic metabolism, but this requires confirmation. If NIR illumination can be further optimized, it may potentially become a useful tool in situations in which glycolysis and platelet activation are exacerbated.

Photobiomodulation of Gingival Cells Challenged with Viable Oral Microbes.

The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs' response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures.

Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer’s disease-associated pathology and cognition in mice

Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aβ) clearance, which is considered as a potential therapeutic target for Alzheimer’s disease (AD). In this study, based on the superficial spatial distribution of mLVs, a near-infrared light is employed to modulate lymphatic drainage, significantly improving cognition of both aged and AD (5xFAD and APP/PS1) mice, and alleviating AD-associated pathology by reducing Aβ deposition, neuroinflammation and neuronal damage. Furthermore, transmission electron microscopy imaging and RNA sequencing data indicate amelioration of mitochondrial metabolism and cellular junction of meningeal lymphatic endothelial cells (mLECs) by light modulation. These studies collectively suggest that near-infrared light treatment can improve cognitive function by strengthening scavenging ability of mLVs through restoring mLEC function. In conclusion, lymphatic drainage potentiation by light promotes pathological remission and cognitive enhancement in aging and AD mouse models, which offers a potential amelioration strategy for neurodegenerative diseases.

Near-Infrared Light Exposure Triggers ROS to Downregulate Inflammatory Cytokines Induced by SARS-CoV-2 Spike Protein in Human Cell Culture.

The leading cause of mortality from SARS-CoV-2 is an exaggerated host immune response, triggering cytokine storms, multiple organ failure and death. Current drug- and vaccine-based therapies are of limited efficacy against novel viral variants. Infrared therapy is a non-invasive and safe method that has proven effective against inflammatory conditions for over 100 years. However, its mechanism of action is poorly understood and has not received widespread acceptance. We herein investigate whether near-infrared (NIR) light exposure in human primary alveolar and macrophage cells could downregulate inflammatory cytokines triggered by the SARS-CoV-2 spike (S) protein or lipopolysaccharide (LPS), and via what underlying mechanism. Our results showed a dramatic reduction in pro-inflammatory cytokines within days of NIR light treatment, while anti-inflammatory cytokines were upregulated. Mechanistically, NIR light stimulated mitochondrial metabolism, induced transient bursts in reactive oxygen species (ROS) and activated antioxidant gene transcription. These, in turn, downregulated ROS and inflammatory cytokines. A causal relationship was shown between the induction of cellular ROS by NIR light exposure and the downregulation of inflammatory cytokines triggered by SARS-CoV-2 S. If confirmed by clinical trials, this method would provide an immediate defense against novel SARS-CoV-2 variants and other inflammatory infectious diseases.

Recent Mechanisms of Neurodegeneration and Photobiomodulation in the Context of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease and the world's primary cause of dementia, a condition characterized by significant progressive declines in memory and intellectual capacities. While dementia is the main symptom of Alzheimer's, the disease presents with many other debilitating symptoms, and currently, there is no known treatment exists to stop its irreversible progression or cure the disease. Photobiomodulation has emerged as a very promising treatment for improving brain function, using light in the range from red to the near-infrared spectrum depending on the application, tissue penetration, and density of the target area. The goal of this comprehensive review is to discuss the most recent achievements in and mechanisms of AD pathogenesis with respect to neurodegeneration. It also provides an overview of the mechanisms of photobiomodulation associated with AD pathology and the benefits of transcranial near-infrared light treatment as a potential therapeutic solution. This review also discusses the older reports and hypotheses associated with the development of AD, as well as some other approved AD drugs.

Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.

Terminalia chebula Polyphenol and Near-Infrared Dye-Loaded Poly(lactic acid) Nanoparticles for Imaging and Photothermal Therapy of Cancer Cells.

Photothermal/photodynamic therapies (PTT/PDT) are multimodal approaches employing near-infrared (NIR) light-responsive photosensitizers for cancer treatment. In the current study, IR-775, a hydrophobic photosensitizer, was used in combination with a polyphenols (p)-rich ethyl acetate extract from Terminalia chebula to treat cancer. IR-775 dye and polyphenols were encapsulated in a poly(lactic acid) polymeric nanosystem (PpIR NPs) to increase the cell bioavailability. The hydrodynamic diameter of PpIR NPs is 142.6 ± 2 nm and exhibited physical stability. The nanosystem showed enhanced cellular uptake in a lung cancer cell line (A549). Cell cytotoxicity results indicate that PpIR NPs showed more than 82.46 ± 3% cell death upon NIR light treatment compared to the control groups. Both PDT and PTT generate reactive oxygen species (ROS) and cause hyperthermia, thereby enhancing cancer cell death. Qualitative and quantitative analyses have depicted that PpIR NPs with NIR light irradiation have decreased protein expression of HSP70 and PARP, and increased γ-H2AX, which collectively lead to cell death. After NIR light irradiation, the relative gene expression patterns of HSP70 and CDK2Na were also downregulated. Further, PpIR NPs uptake has been studied in 3D cells and in ovo bioimaging in zebrafish models. In conclusion, the PpIR NPs show good cancer cell cytotoxicity and present a potential nanosystem for bioimaging.

Facile synthesis of black phosphorus-zinc oxide nanohybrids for antibacterial coating of titanium surface

Bacterial infection is a major complication associated with bioimplant materials, including titanium (Ti) based orthopedic joints and dental implants. Thus, the fabrication of Ti surfaces with antibacterial activity is highly important. Black phosphorus (BP) is a recently discovered promising two-dimensional semiconductor for various biomedical applications due to its tunable bandgap and physicochemical properties. The present study aimed to synthesize zinc oxide (ZnO) laden BP nanohybrids (NH) and their coatings on a Ti bioimplant surface for improving the antibacterial activities against pathogenic bacteria with and without near-infrared (NIR) light irradiation. Nanohybrids were produced with the slightly oxidized BP NF and electrostatically laden ZnO NP. The produced BP-ZnO NH was a NIR active nanomaterial (up to ∼1000 nm), demonstrating a photothermal effect against bacterial infection and showing improved activity by damaging the cell membrane towards S. aureus in comparison to E. coli. Ti surface coated with BP-ZnO NH embedded chitosan (CS) demonstrated better antibacterial activity than BP NF, especially with NIR light treatment. Additionally, the produced BP nanoflakes and BP-ZnO NH, and their coatings over the Ti surface were found to be toxic at a negligible level. Electrochemical studies revealed the high corrosion resistance of the Ti surface coated with the synthesized antibacterial agents without altering its characteristic passive behavior. Owing to the interactions between the charged groups between chitosan and cell surfaces, a slight increase in antibacterial activities was noticed. Chitosan-based coating matrix embedded with nanoagents has adhered well over the Ti surface due to its inherent film-forming and high adhesion properties.

Efficacy of Transcranial Near-Infrared Light Treatment in ASD: Update on Open-Label Proof of Concept Study of a Novel Approach

ASD is characterized by variable presentation of difficulties with socialization, communication, and restrictive/repetitive behaviors (RRBs), for which no established pharmacological treatment exists. Transcranial laser emitting diode (LED) therapy (TLT) is a noninvasive intervention with near-infrared light to the forebrain. It is absorbed by cytochrome c oxidase in mitochondria and increases energy metabolism, leading to cellular plasticity and cytoprotection. Recently, TLT was found to be safe and effective in the treatment of depression.

T65. Efficacy of Transcranial Near-Infrared Light Treatment in ASD: Interim Analysis of an Open-Label Proof of Concept Study of a Novel Approach

T65. Efficacy of Transcranial Near-Infrared Light Treatment in ASD: Interim Analysis of an Open-Label Proof of Concept Study of a Novel Approach

5.20 Efficacy of Transcranial Near-Infrared Light Treatment in ASD: Interim Analysis of an Open-Label Proof of Concept Study of a Novel Approach

ASD is characterized by variable presentation of difficulties with socialization, communication, and restrictive/repetitive behaviors (RRB), for which no established pharmacological treatment exists. Transcranial Laser Emitting Diode (LED) Therapy (TLT) is a noninvasive intervention with near-infrared light to forebrain. It is absorbed by cytochrome c oxidase in mitochondria and increases energy metabolism, leading to cellular plasticity and cytoprotection. Recently, TLT was found to be safe and effective in the treatment of depression. Effects of TLT on ASD symptoms remains to be explored.

Near Infrared Light Treatment Reduces Synaptic Levels of Toxic Tau Oligomers in Two Transgenic Mouse Models of Human Tauopathies

Tau oligomers are emerging as a key contributor to the synaptic dysfunction that drives cognitive decline associated with the clinical manifestation and progression of Alzheimer’s disease (AD). Accordingly, there is ample consensus that interventions that target tau oligomers may slow or halt the progression of AD. With this ultimate goal in mind, in the present study, we investigated tau oligomer accumulation and its synaptic and behavioral consequences after an in vivo treatment with near infrared (NIR) light (600–1000 nm) in two transgenic mouse models, overexpressing human tau either alone (hTau mice) or in combination with amyloid beta (3xTgAD mice). We found that a 4-week exposure to NIR light (90 s/day/5 days a week) significantly reduced levels of endogenous total and oligomeric tau in both synaptosomes and total protein extracts from the hippocampus and cortex of hTau mice and improved deteriorating memory function. Similar results were observed in the 3xTgAD mice, which further displayed reduced synaptic Aβ after NIR light treatment. On the other hand, ex vivo binding of tau oligomers in isolated synaptosomes as well as tau oligomer-induced depression of long-term potentiation (LTP) in hippocampal slices from NIR light-treated wt mice were unaffected. Finally, levels of proteins critically involved in two mechanisms associated with clearance of misfolded tau, inducible HSP70 and autophagy, were upregulated in NIR light treated mice. Collectively, these results show that NIR light decreases levels of endogenous toxic tau oligomers and alleviate associated memory deficits, thus furthering the development of NIR light as a possible therapeutic for AD.

Acute Effects of Near Infrared Light Therapy on Brain State in Healthy Subjects as Quantified by qEEG Measures.

Recent investigation suggests that near infrared (NIR) light may improve symptoms from mild traumatic brain injury. In addition, quantitative electroencephalography (qEEG) has shown measures correlating with concussion: P300, reaction time, and amplitude. The objective of this study was to determine whether NIR light treatment has an acute effect on brain state in healthy patients as measured by EEG. A total of 31 healthy volunteers, between the ages of 14 and 65, underwent qEEG event-related response tests before and after a 20-min NIR light head treatment. The treatment device is composed of 784 NIR GaAIAs LEDs covering 360 cm2 on the head in a cap covering occipital, left temporal, right temporal frontal, and parietal lobes. The fluence rate was 1 J/cm2·min for a power density of 16.67 mW/cm2. Peak spectral wavelength at steady-state temperature (42.2°C) is 903 nm. The device delivered a total dose of 20 J/cm2. Two to four months later, 18 subjects returned for a second round of qEEG measurements, with a 20-min rest period in place of the NIR light treatment as a control arm. Change in reaction time significantly differed between treated and control, with a mean of 23.8 msec improvement compared with controls (p = 0.035). Amplitude increased an average of 0.81 μV in treatment versus 0.22 μV in controls and did not reach significance. However, subanalysis of 14 treated subjects and 8 controls displaying initially low amplitude showed a mean increase in amplitude of 1.83 μV (30%) in treated subjects versus 0 μV in controls (p = 0.08). P300 measures did not show significant differences between groups. The data suggest that NIR light may have an acute effect on reaction time and amplitude in certain subject subsets. There were no adverse events registered across the 31 subjects in the treatment group, nor in the 18 evaluable control group subjects.

Near-infrared light treatment reduces astrogliosis in MPTP-treated monkeys.

We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (containing the substantia nigra pars compacta; SNc) and striatum were processed for glial fibrillary acidic protein (to label astrocytes; GFAP) and ionised calcium-binding adaptor molecule 1 (to label microglia; IBA1) immunohistochemistry. Cell counts were undertaken using stereology, and cell body sizes were measured using ImageJ. Our results showed that NIr treatment reduced dramatically (~75%) MPTP-induced astrogliosis in both the SNc and striatum. Among microglia, however, NIr had a more limited impact in both nuclei; although there was a reduction in overall cell size, there were no changes in the number of microglia in the MPTP-treated monkeys after NIr treatment. In summary, we showed that NIr treatment influenced the glial response, particularly that of the astrocytes, in our monkey MPTP model of Parkinson's disease. Our findings raise the possibility of glial cells as a future therapeutic target using NIr.

Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson's Disease.

Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn) in the substantia nigra of an AAV-based rat genetic model of Parkinson’s disease (PD). In this model, daily exposure of both sides of the rat’s head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies.

A Controlled Trial to Determine the Efficacy of Red and Near-Infrared Light Treatment in Patient Satisfaction, Reduction of Fine Lines, Wrinkles, Skin Roughness, and Intradermal Collagen Density Increase

The purpose of this study was to investigate the safety and efficacy of two novel light sources for large area and full body application, providing polychromatic, non-thermal photobiomodulation (PBM) for improving skin feeling and appearance. For non-thermal photorejuvenation, laser and LED light sources have been demonstrated to be safe and effective. However, lasers and LEDs may offer some disadvantages because of dot-shaped (punctiform) emission characteristics and their narrow spectral bandwidths. Because the action spectra for tissue regeneration and repair consist of more than one wavelength, we investigated if it is favorable to apply a polychromatic spectrum covering a broader spectral region for skin rejuvenation and repair. A total of 136 volunteers participated in this prospective, randomized, and controlled study. Of these volunteers, 113 subjects randomly assigned into four treatment groups were treated twice a week with either 611-650 or 570-850 nm polychromatic light (normalized to ∼ 9 J/cm(2) in the range of 611-650 nm) and were compared with controls (n=23). Irradiances and treatment durations varied in all treatment groups. The data collected at baseline and after 30 sessions included blinded evaluations of clinical photography, ultrasonographic collagen density measurements, computerized digital profilometry, and an assessment of patient satisfaction. The treated subjects experienced significantly improved skin complexion and skin feeling, profilometrically assessed skin roughness, and ultrasonographically measured collagen density. The blinded clinical evaluation of photographs confirmed significant improvement in the intervention groups compared with the control. Broadband polychromatic PBM showed no advantage over the red-light-only spectrum. However, both novel light sources that have not been previously used for PBM have demonstrated efficacy and safety for skin rejuvenation and intradermal collagen increase when compared with controls.

Effect of near-infrared light exposure on mitochondrial signaling in C2C12 muscle cells

Near-infrared (NIR) light is a complementary therapy used to treat musculoskeletal injuries but the underlying mechanisms are unclear. Acute NIR light treatment (~800–950nm; 22.8J/cm2) induced a dose-dependent increase in mitochondrial signaling (AMPK, p38 MAPK) in differentiated muscle cells. Repeated NIR light exposure (4days) appeared to elevate oxidative stress and increase the upstream mitochondrial regulatory proteins AMPK (3.1-fold), p38 (2.8-fold), PGC-1α (19.7%), Sirt1 (26.8%), and reduced RIP140 (23.2%), but downstream mitochondrial regulation/content (Tfam, NRF-1, Sirt3, cytochrome c, ETC subunits) was unaltered. Our data indicates that NIR light alters mitochondrial biogenesis signaling and may represent a mechanistic link to the clinical benefits.

Survival of Dopaminergic Amacrine Cells after Near-Infrared Light Treatment in MPTP-Treated Mice.

We examined whether near-infrared light (NIr) treatment (photobiomodulation) saves dopaminergic amacrine cells of the retina in an acute and a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. For the acute model, BALB/c mice had MPTP (100 mg/kg) or saline injections over 30 hours, followed by a six-day-survival period. For the chronic model, mice had MPTP (200 mg/kg) or saline injections over five weeks, followed by a three-week-survival period. NIr treatment was applied either at the same time (simultaneous series) or well after (posttreatment series) the MPTP insult. There were four groups within each series: Saline, Saline-NIr, MPTP, and MPTP-NIr. Retinae were processed for tyrosine hydroxylase (TH) immunochemistry, and cell number was analysed. In the MPTP groups, there was a significant reduction in TH+ cell number compared to the saline controls; this reduction was greater in the acute (~50%) compared to the chronic (~30%) cases. In the MPTP-NIr groups, there were significantly more TH+ cells than in the MPTP groups of both series (~30%). In summary, we showed that NIr treatment was able to both protect (simultaneous series) and rescue (posttreatment series) TH+ cells of the retina from parkinsonian insult.

Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice

We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN) and zona incerta (ZI); both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100–250 mg/kg) or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model) or over five weeks followed by a three-week survival period (chronic model). NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30–45%) the increase in Fos+ cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number). In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

Near Infrared Light Reduces Oxidative Stress and Preserves function in CNS Tissue Vulnerable to Secondary Degeneration following Partial Transection of the Optic Nerve

Traumatic injury to the central nervous system (CNS) is accompanied by the spreading damage of secondary degeneration, resulting in further loss of neurons and function. Partial transection of the optic nerve (ON) has been used as a model of secondary degeneration, in which axons of retinal ganglion cells in the ventral ON are spared from initial dorsal injury, but are vulnerable to secondary degeneration. We have recently demonstrated that early after partial ON injury, oxidative stress spreads through the ventral ON vulnerable to secondary degeneration via astrocytes, and persists in the nerve in aggregates of cellular debris. In this study, we show that diffuse transcranial irradiation of the injury site with far red to near infrared (NIR) light (WARP 10 LED array, center wavelength 670 nm, irradiance 252 W/m(-2), 30 min exposure), as opposed to perception of light at this wavelength, reduced oxidative stress in areas of the ON vulnerable to secondary degeneration following partial injury. The WARP 10 NIR light treatment also prevented increases in NG-2-immunopositive oligodendrocyte precursor cells (OPCs) that occurred in ventral ON as a result of partial ON transection. Importantly, normal visual function was restored by NIR light treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and the Y-maze pattern discrimination task. To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo.