Mechanisms of Photobiomodulation Therapy XIX

We proposes Reversibility-based Photomedical Classification System (RbPCS), aiming to integrate and standardize photomedical terminology including Photobiomodulation. We classify concepts based on two factors: (1) reversibility of light-induced chromophores, (2) reversibility of chromophore-mediated cellular effect. Additionally, RbPCS have three optional affixes to indicate the perspective of action: (1) Endo- (Endogenous) and Exo- (Exogenous), (2) Rm-, Rd-, Ru-, (Recognition mediated/dependent/unrelated), (3) -T (Therapy). RbPCS is formulized by photons, chromophores, energy exchange, tissue, chromophore effect, and cellular effects. This framework provides the equations for optimizing light parameters in specific therapeutic contexts.

The four major Chronic Noncommunicable Causes of Death—Atherosclerotic Cardiovascular Disease, Cancer, Neurodegenerative Diseases, and Type 2 Diabetes, along with related metabolic dysfunction—pose significant personal and costly public health challenges. Preventative strategies typically emphasise diet, exercise, and sleep. This presentation explores the potential role of photobiomodulation (PBM) in enhancing these lifestyle interventions. PBM has been clinically proven to enhance exercise performance, improve sleep quality, reduce hypertension, and mitigate oxidative damage. These benefits could help delay the onset and progression of the aforementioned chronic diseases. Moreover, PBM has been shown to improve heart rate variability (HRV), lower resting heart rate, and increase VO2 Max, all of which are associated with a reduced risk of all-cause mortality. Integrating photobiomodulation into a suite of validated healthy lifestyle choices could play a significant role in delaying the onset and progression of the four leading Chronic Noncommunicable Causes of Death.

Proper healing is essential to preserve tissue homeostasis and protect the body from the external environment. Nowadays, physical therapies are recognized among the standard approaches for the treatment of chronic wounds. The mechanism underlying the effectiveness of the application of laser or LED sources is not yet fully clarified. Here, we show the results of in vitro studies conducted using a device based on LED technology emitting a range of wavelengths between 410 and 430 nm (1 W optical emission power) on cultured cells. Different doses of blue light (4 - 21 - 42 J/cm2) were applied. MicroRaman spectroscopy and patch clamp recordings were used to study the redox state of cells and ionic membrane currents modulated by blue light, respectively. Confocal microscopy was used to reveal ROS fluctuations. Our results show that blue light induces photobiomodulation in a dose-dependent manner.

Photobiomodulation therapy (PBMt) is gaining popularity as a non-invasive treatment that leverages light to enhance cellular function and promote healing. This paper explores the potential of PBMt to meet the healthcare and wellness needs of the MZ generation (Millennials and Generation Z), who are increasingly seeking holistic and preventive health solutions. Applications of PBMt in skin care, mental health, pain management, and fitness recovery are particularly relevant to this demographic. Technological advancements, such as wearable and home-use PBMt devices, have made the therapy more accessible and convenient. As awareness and research continue to grow, PBMt is poised to become a mainstream solution for various health concerns, offering a natural and effective alternative to traditional treatments.

Photobiomodulation (PBM) is a non-invasive therapy that uses low-level laser light to promote healing and reduce inflammation. The technique's effectiveness depends on how light is absorbed and scattered in tissues, which influences temperature distribution. This study uses Monte Carlo (MC) simulations in MATLAB to model temperature changes in skin tissue during PBM, considering the effects of scattering and absorption in different layers, such as the epidermis, dermis, adipose tissue, and blood vessels. The findings offer insights into optimizing PBM treatment protocols, ensuring effective therapy while minimizing the risk of thermal damage.

Photobiomodulation (PBM) offers a non-invasive, non-thermal therapeutic approach using red and near-infrared light within the 600-1,100 nm range. While wavelength selection is vital, optimal outcomes require a comprehensive understanding of light dosimetry, to further calculate fluence rate on tissue interactions. This study evaluates two FDA-approved PBM devices at 660nm and 810nm, using advanced modeling to analyze light distribution and absorption. By refining our approach to light PBM dosimetry, these findings will support enhanced clinical protocols and drive progress in PBM therapy across medicine and dentistry.

hotostimulation and photobiomodulation (PBM) can be studied at the cellular level. Photostimulation increases growth and metabolism in healthy cells while photobiomodulation typically reverses a pathological state. Perturbations in mitochondrial bioenergetics and cytoskeleton components are processes likely to occur in both photostimulation and PBM. Here, we studied the cellular responses to low-intensity light using confocal, low-frequency Raman microscopy. Wavelength and dosimetry of experimental lasers (450, 635, 808 nm) were varied to determine important laser determinants for inducing cellular responses. Both epithelial and neural cell cultures were studied, providing common and unique features for the analysis of biological mechanisms underlying photon-cell interactions.

We have previously shown a stimulation of enzyme activity for complex IV of the electron transport chain in isolated mitochondria after exposure to 2.52 terahertz (THz) radiation. The dose-dependent enhancement was substantial, but the effect was not fully characterized due to constraints of the THz laser. Here, we used a different THz laser to characterize this photostimulation, using adenosine triphosphate (ATP) production and mitochondrial membrane potential as end points of analyses. We compare the stimulation at 2.52 THz with efficiencies at other THz frequencies. The results indicated that an ordered structure of water is required for biological activity.

We investigated the effects of optical vortex and photobiomodulation on Parkinson's disease (PD) model cells by quantitatively assessing PD-related proteins after laser irradiation. Current treatments for Parkinson's disease are symptomatic, involving drugs or surgery, both of which concern invasive and non-causal treatment. We propose a minimally invasive therapy using optical vortex irradiation and photobiomodulation that can activate biological responses without damaging cells. PBM can reduce oxidative stress and restore normal cell function in PD. Our study on SH-SY5Y cells overexpressing α-synuclein showed that optical vortex irradiation significantly reduced α-synuclein levels, suggesting its potential to reduce PD-causing proteins and promote dopamine production. These results suggested that Antioxidant stress which was induced by laser irradiation might decline causative protein of Parkinson’s disease.

It has been widely reported that the gut-brain axis is an important link in Parkinson’s disease, where gastric problems, such as gut motility issues, constipation and diarrhea can occur years before neurological diagnosis of the disease. There is accumulating evidence that photobiomodulation is a potential therapy to slow or even reverse some of the motor and non-motor symptoms of Parkinson’s disease over several years. We have previously shown that not only transcranial photobiomodulation with LEDs but also laser photobiomodulation to the abdomen and neck can improve motor and non-motor symptoms of Parkinson’s disease. We have also shown that photobiomodulation can alter the microbiome in mice and may also affect changes in the microbiomes of people with Parkinson’s disease. In this presentation we will examine the changes in the microbiome of a small cohort of participants in a Parkinson’s disease study who have continued photobiomodulation therapy for 5 years, with changes in the proportions of both the bacteria occurring in parallel to the retardation of normal symptom progression of Parkinson’s disease.

Current methods to treat pain have several limitations (e.g., addiction, limited efficacy, etc.) and new options are sorely needed. Transient Selective Neural Inhibition via Photobiomodulation (tSNIP) at 808 nm has been shown to reduce small-fiber axon sensitivities in both human and animal models when applied to block action potentials. A study focused on optimizing parameters for sensitivity reduction was conducted. Results showed a reduction in pain lasting about 8 days, indicating that there are certain combinations of light that are more optimal.

OBJECTIVES: To evaluate the efficacy, safety, and compliance of laser-acupuncture in children with autism spectrum disorder (ASD). DESIGN: Randomized, sham controlled, double blind trial, with blinded evaluation, statistical analysis of results and standardized parent report

Background: Photobiomodulation (PBM) therapy utilizing red and near-infrared light (600-1,100nm) is gaining prominence as a non-invasive treatment modality in dentistry. The effect of tissue structure on light transmission, particularly in the context of clinical dentistry, remains underexplored. This preliminary study aims to investigate the impact of a soft tissue flap on the transmission of 660nm and 810nm light sources through cortical bone, providing insights for future applications in periodontal and maxillofacial surgery. Materials and Methods: Porcine mandibular bone was used as a model to simulate human cortical bone, with soft tissue flaps placed over a cortical bone sample. Light from 660nm and 810nm devices was applied and measured using an isotropic detector. The resulting fluence rate was calculated in mW/cm2. Statistical analysis will be performed to evaluate the mean and standard deviations for each parameter. Results: Preliminary data indicates that the soft tissue flap significantly reduces light transmission at both wavelengths. These findings suggest that the depth of light penetration and tissue absorption characteristics differ between red and near-infrared

Rotator cuff tears are a leading cause of upper extremity pain and disability, making them the most frequent tendon injury among adults. Recovery times vary based on the tear's size, ranging from 3 to 6 months, and up to 1 year for extensive tears. Most patients resume work around 8 months post-surgery. Photobiomodulation (PBM) utilizing LED (light emitting diodes) or laser light sources is currently the subject of extensive research due to its potential to speed up tissue healing and regeneration, as well as provide pain relief. In this study, we integrated conventional physiotherapy methods with our multimodal PBM protocol, administering treatments once a week. Guidelines for treating these injuries are well established. By applying our protocol with just one session per week, we achieved recovery within 8 weeks. With this work we aim to take a step further to establish new protocol procedures in this kind of injuries.

While there has been a number of studies that show the effect of photobiomodulation on the cytoskeleton in the peripheral nervous system, there are few studies that address the interaction of PBM and the cytoskeleton of the central nervous system. A perspective was developed that incorporated recent literature on the role of the cytoskeleton and the potential interaction with photobiomodulation to explain the effects of PBM that are seen with transcranial and other PBM applications. We propose that conformational changes to the cytoskeleton (including varicosities) is a mechanism of photobiomodulation that is additional to its other known effects. The reversible changes to the cytoskeleton in peripheral and central nerve cells may be one mechanism underlying pain relief by photobiomodulation intervention. This proposed mechanism has potential implications for pathologies involving cytoskeletal dysfunctions, such as chronic pain, dysregulated immune responses (mastocytosis) and chronic renal disease.

We recently discovered that noninvasive low-level laser (LLL) could shift the metabolic balance toward oxidative phosphorylation, substantially enhancing the number and function of tumor-infiltrated CD8+ T cells. LLL irradiation on tumors and draining lymph nodes resulted in increased survival of these CD8+ T cells, prolonged their effective phase, and promoted their memory cell development. Additionally, LLL treatment augmented natural killer (NK) cells, improving both their number and functionality. The cellular enhancements were also corroborated by single-ell RNA sequencing (ScRNA seq), showing increases of expressing genes associated with mitochondrial functions, cytotoxicity, survival, and memory of CD8+ T cells and NKs. When combined with an agonist of the stimulator of interferon genes (STINGa), LLL applied to both tumor and draining lymph nodes synergistically eliminated lymphoma.

Photobiomodulation therapy (PBMT) using a low-energy density visible to near-infrared laser is an innovative physiotherapy technique. An increasing number of experimental and clinical studies have demonstrated that PBMT has a positive impact on reducing pain and inflammation, promoting wound healing, and enhancing tissue regeneration. Some research evidence also indicates that PBMT has a protective effect on cardiovascular disease, though the underlying mechanisms remain unclear. In this study, we loaded mouse primary peritoneal macrophages with oxLDL to simulate a foam cell model and then treated them with a 633 nm laser (8 J/cm²) for 5 minutes to explore the effect of PBMT on the lipid content of foam cells. Lipid staining revealed that cells treated with PBMT had less lipid content compared to the control. Further results suggested that PBMT promotes ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from macrophages. The underlying molecular mechanism may involve the upregulation of ABCA1 expression. This study may offer a viable method to inhibit foam cell formation and control the progression of atherosclerosis.

Platelet-rich plasma (PRP) therapy, which enhances tissue repair and regeneration by concentrating platelets and growth factors, relies heavily on effective activation of these growth factors. Traditional activation methods, such as thrombin or calcium chloride, lack control and efficiency. Our study introduces a novel PRP activation approach using specific wavelengths of light (660-830 nm) at various fluences to induce growth factor release more effectively. We developed a device with LED light sources, source management electronics, circuitry, and an LCD touchscreen, housed in a 3D-printed polymer casing. PRP, prepared from patient blood by centrifugation, is exposed to these wavelengths to activate platelets and release growth factors like PDGF, TGF-β, and VEGF. The efficacy of this method is assessed using ELISA and other biochemical tests. Light-activated PRP may offer superior regenerative potential and broader therapeutic applications, presenting an efficient and controlled alternative to current PRP therapies.

Photobiomodulation (PBM) is a regulatory approach that utilizes red or near-infrared light to promote tissue repair and blood microcirculation, thereby generating positive therapeutic effects at multiple levels. In recent years, as an emerging non-invasive therapy, PBM has been widely applied in the modulation of neurodegenerative diseases. However, due to the high scattering and light absorption characteristics of the skull and the incomplete understanding of the intracranial propagation properties of light at different wavelengths, the application of optical techniques in transcranial modulation is greatly limited. Therefore, in order to optimize the light therapeutic efficacy of brain diseases, there is an urgent need to investigate the physical properties of light transcranial spread. In this work, the transmittance of transcranial lasers with wavelengths of 660 nm and 808 nm at different positions of skulls from various strains of mice were detected and compared. Furthermore, the skull thickness dependence of light penetration through skull was investigated by fitting analysis, providing data support for establishing the optimal therapeutic strategy of transcranial PBM.

Recent Alzheimer's disease (AD) studies have demonstrated that light stimulation (LS) can effectively inhibit the progression of amyloid-β (Aβ) plaque (the main hallmark of AD) growth and activate the immune response. Despite these findings, the underlying mechanisms of LS require further exploration. Our research delves into these effects by employing biophotonic imaging and therapeutic modalities within an AD mouse model. Utilizing advanced two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS) microscopy, we observed a reduction in both Aβ plaques and cerebral amyloid angiopathy following LS treatment. Additionally, 3D immunofluorescence imaging of brain slices showcased a decrease in Aβ plaque density accompanied by microglial accumulation around the plaques post-LS treatment. Concurrently, the Morris water maze test indicated significant improvements in the spatial learning and memory capabilities of the AD mice after LS. These findings offer valuable insights for the development of sophisticated optical imaging technologies and the optimization of LS parameters, potentially leading to more effective monitoring and phototherapy strategies.

Photobiomodulation and photonic therapies often lead to increased local temperature due to irradiation, and separating the photothermal effects can be challenging. In this study, we focus on the analysis of thermal effects on mitochondria using thermal conduction, aiming to correlate the temperature increase with the incubation time. The effects were investigated in vitro using high-resolution respirometry with permeabilized hepatocytes and mitochondria isolated from mouse liver. Our results reinforce the importance of considering both temperature and exposure time when analyzing thermal effects, and also that the cellular machinery protects the mitochondrial from thermal damage. These findings are preliminary, and we aim to further compare the effects of pure thermal conduction to photothermal effects.

Glaucoma, a leading cause of irreversible blindness, is characterized by a progressive degeneration of retinal ganglion cells (RGCs). Current therapies mainly reduce intraocular pressure (IOP) but offer limited protection against retinal excitotoxicity, a key factor in neuronal loss caused by imbalanced excitatory and inhibitory transmission (E/I imbalance). This study aims to target excitotoxicity via modulating E/I imbalance within the retina as a potential therapeutic approach to minimize physical damage in glaucoma. Using an ischemia-reperfusion (I/R) mouse model which induced elevated IOP, we administered an excitotoxic modulator to the treatment group 10 minutes post-I/R. After one week of daily treatment, retinal morphology and RGC numbers were quantified using hematoxylin and eosin staining and immunohistochemistry. Treated eyes showed better preservation of retinal structure and less RGC loss compared to controls, suggesting a neuroprotective effect against retinal excitotoxicity. These results highlight the neuroprotective role of the modulator in reducing retinal degeneration under elevated IOP conditions, suggesting its potential as a therapeutic approach for glaucoma.