Photobiomodulation: How various life forms respond to light

Seshadri Dutta, NIIT University

Introduction

Recently, there has been a major interest in using laser therapy in health and dentistry. There are various types of lasers available, and their applications are well defined by parameters such as wavelength, energy density, power output, and radiation duration. For example, light interacts with photosensitive cells in our retinas called photoreceptors to give us vision.

Early development of photonic applications was hindered by plenty of issues, including a lack of consistency in terminology. A variety of terms were introduced like Biostimulation, Cold/Cool Laser, Low- Level laser therapy, Soft Laser, and Low Power Laser Therapy. In 2015 due to the efforts of Dr. Praveen Arany, PBMT was added to the National Library of medication database as an entry term to the current record of laser therapy, low-level.

Understanding Photobiomodulation

Laser therapy has changed dramatically since its inception in the early 1960s. The use of non-ionizing electromagnetic energy to induce photochemical changes within photoreceptive cellular structures by utilizing sources in the visible (400 – 700 nm) and near-infrared range (700 – 1100 nm), such as LASERS, LEDs, and broadband light is known as photobiomodulation treatment. Photobiomodulation (PBM) can also be described as the manipulation of biosystems using laser irradiation, monochromatic light, hot colour light like red, orange, or yellow, or cold colour light like green, blue, or violet (LI).

Mechanism

A light source is positioned near or in touch with the skin, allowing photons to penetrate tissue and interact with chromophores in cells, causing photophysical and photochemical changes that cause changes at the molecular and cellular levels. In the injured tissues, light triggers a complex sequence of physiological reactions that speed wound healing and tissue regeneration, improve circulation, reduce acute inflammation, relieve acute and chronic pain, and restore normal cellular function.

Endogenous chromophores induce photophysical and photochemical processes at diverse biological scales in this non-thermal mechanism.

Process

The receptive organelle for this process is the mitochondria. At the cellular level, mitochondria absorb visible red and NIR, which are responsible for producing cellular energy known as “ATP.” When performing below par, a mitochondrial enzyme called cytochrome oxidase c, a chromophore that takes photonic energy of specific wavelengths, is the key to the entire process. Photons enter the tissue, get scattered, absorbed and they interact with the cytochrome c complex within mitochondria, triggering a biochemical signaling cascade that results in an increase in cellular metabolism, reducing pain and speeding up the healing process.

I. Cytochrome C stimulation

The Cytochrome C complex, situated in the inner membrane of the cell mitochondria, is the major target for photobiomodulation and an important part of the electron transport chain, also responsible for cellular metabolism.

II. Increased production of ATP

The electron transport chain is stimulated by light absorption by Cytochrome C oxidase, thus increasing ATP generation within mitochondria. When tissue is destroyed, the cell’s ability to produce ATP is compromised, slowing the cell’s metabolism as a protective measure. PBM aids in the restoration of the oxidative process, therefore rehabilitating normal cellular activity.

III. Increase NO and ROS activity

Laser stimulation generates free nitric oxide (NO) and regulates reactive oxygen species (ROS) in addition to ATP. NO is a potent vasodilator and a key cellular signaling molecule involved in a wide range of physiological functions. Many essential physiological signaling pathways, including the inflammatory response, have been demonstrated to be influenced by ROS. Increased NO and better ROS levels together create a favorable environment for quicker signaling, leading to a reduction in inflammation.

IV. Cellular Energy Balance Restoration

Photobiomodulation (PBM) aids in restoration of normal cellular activity, hence preventing apoptosis (cell death). This aids in the reduction of inflammation and edema, as well as accelerated tissue repairing.

Clinical Applications of Photobiomodulation Therapy

Photobiomodulation therapy (PBMT) has a wide range of applications, which are being investigated experimentally at the basic research, preclinical, and clinical levels. Current clinical applications include pain and inflammatory alleviation, also treatment of sports injuries. The FDA has approved PBMT devices for stimulating hair growth and reducing fat accumulation.

• Targeting inflammation

PBMT reduces inflammation by increasing the size of the body’s smaller arteries and lymph vessels, a process known as vasodilation. Vasodilation facilitates the removal of inflammation, swelling, and edoema from injury sites. Lymphatic drainage is aided by lymphatic vasodilation in lymph nodes, which aids in the healing process.

• Pain relief

A clinician must diagnose the issue before employing PBMT treatment to treat acute or chronic pain to ensure that the pain is caused by a neuromusculoskeletal condition induced by ageing or injury and there are no contraindications of laser use. Pregnant women should avoid PBMT as the effects on the foetus are uncertain. For optimal pain alleviation, PBMT usually takes multiple treatments. The effects may take several treatments to become apparent.

Application of PBMT on Mammalian Hosts

Laser therapy using PBM has yet to be included in a standardised treatment for tissue repair and regeneration. It is a non-invasive treatment, found to reduce inflammation and relieve pain. Treatments of Tendinopathies, nerve injuries, osteoarthritis, and wound healing might all benefit from the use of laser therapy to tissues. Mild side effects of the therapy include cutaneous irritation, itching, and redness, which aren’t dangerous and don’t raise the temperature of target tissue. The influence of PBM on vulnerable stem cells and progenitor cells, and its potential for promoting differentiation and increasing tissue healing rates, is a significant area of research.

PBM also shows enhanced stem cell proliferation in a variety of investigations, including dental pulp stem cells isolated from permanent teeth, exfoliated deciduous teeth, and mesenchymal stem cells derived from adipose tissue or bone marrow. It’s medical applications have been demonstrated in laboratory tests to be successful (partially) due to its strong anti-inflammatory properties.

Several scientists evaluated burn wounds in rats using a super pulsed 904 nm laser and revealed quicker healing, reduced inflammation, decreased expression of TNF- and NF-kB, and up-regulated expression of VEGF and FGFR-1.

Arthritis is most commonly caused in humans by a degenerative process, (osteoarthritis) or an autoimmune process (rheumatoid arthritis). Researchers have investigated the effects of two different fluences of 810 nm (3 J/cm2) laser given at two different power densities (5 and 50 mW/cm2) using a zymosan-induced arthritis model and discovered that three of the four sets of parameters were equally efficient in decreasing edoema and PGE2 (Prostaglandin E2) but the ineffective set (3 J/cm2 given at 50 mW/cm2) required one minute of illumination time.

There have also been studies on the effects of PBM on inflammatory pain in animal models. Some research has investigated models of neuropathic pain, known as “spared nerve damage” and found that applying PBM (980 nm) to the injured hind paw improved pain ratings.

Application of PBMT on Non-mammalian Hosts

Since there are essentially no negative effects of PMBT, conducting controlled clinical trials is quite simple. Mammalian cells (normal or cancerous) in culture, small rodents as disease models have always been the focus of laboratory study.

Recently several papers and studies have also shown the application of PBM in so-called “model organisms” including flies (Drosophila), worms (C. elegans), fish (zebrafish) etc. In comparison to vertebrate animals, they are less expensive to operate with and have lesser regulatory obstacles. Although plants may react to NIR light differently from visible light (photosynthesis and photomorphogenesis), PBM in plants has received little attention.

• Mechanism

Bacterial electron transport chains are more complex than those in mammalian mitochondria and are situated in the plasma membrane. For example, ETC of a Gram-negative facultative anaerobe, Paracoccus denitrificans, that lives in soil has four complexes that match those in the mitochondrial chain while developing aerobically. The chain is constructed differently when this bacteria develops anaerobically with nitrate as its electron acceptor.

In case of plants, since chloroplasts and mitochondria are two distinct light-responsive organelles in plants, any disruption will hinder the cell’s metabolism. However, NIR (> 800 nm) is usually thought not to initiate photosynthesis or have any effect on plant cells.

• PBM in Model Organisms or Non-Mammals

The diversity of lifeforms researched is impressive, yet there are a few available at this time. The majority of Russian bacterial photobiomodulation research centred on the Escherichia coli WP2 trp-strain. The studies were mostly conducted with a He-Ne laser (632.8 nm) recorded in different wavelengths. They discovered that after transferring cells from the irradiation buffer to nutritive media, PBM produces a temporary increase in cell division. In cultures with a short latent period, the difference between irradiated and non-irradiated groups was significantly reduced. Some studies using wild-type E coli resulted in unaffected bacterial growth. Furthermore, it has been observed that the PBM effects do not occur in anaerobic conditions as after being exposed to oxygen for 24 hours, anaerobically grown cells again became receptive to PBM growth stimulation. The effects of wavelengths of 660 nm, 830 nm, and 904 nm on Staphylococcus aureus, E.coli, and Pseudomonas aeruginosa were studied and all of these wavelengths indicated inhibition of bacterial growth.

• Plants

Reports in “Hunker” (https://www.hunker.com/) include “According to Texas A&M University, infrared light plays a part in the blooming of flowering plants. Plants grown indoors may grow well under fluorescent lights, but will not bloom until appropriate levels of infrared radiation have been introduced. This can be done using special horticultural lights, or simply by adding incandescent light bulbs”.

Conclusion and Future scopes

In recent years, therapeutic users of PBM have risen rapidly. It appears that all living forms can somewhat respond to PBM-type treatments. Understanding the molecular and cellular mechanisms of action of PBM has provided a scientific justification for its usage in a variety of illnesses. Though the parameters are known at a basic level, PBM has no recorded negative consequences. However, one of the most widely recognized advantages is its anti-inflammatory properties. Chronic illnesses of the current era including systemic inflammation, such as type 2 diabetes, obesity, Alzheimer’s disease, cardiovascular disease etc. are worth looking into in the context of PBM.

Also due to the lack of studies on application of PBM on plants, assumptions have been created that photosynthesis is driven by red light and thus PBM is not possible. Several researches have shown applications of PBM in poultry and egg production, especially when these activities are now frequently carried out indoors under artificial illumination.

Despite the fact that the biostimulatory impact of lasers is well-established and described by several factors, further study into the possibility of safe therapy is needed.

Also Read: BRAFi-addicted melanoma cells: proteomics and phosphoproteomics profiling

References

1. Michael R. Hamblin. Photobiomodulation or low-level laser therapy. J Biophotonics. 2016 Dec; 9(11-12): 1122–1124. DOI: https://dx.doi.org/10.1002%2Fjbio.201670113
2. Anders, Juanita J. “Photobiomodulation.” American Society for Laser Medicine and Surgery, https://www.aslms.org/for-the-public/treatments-using-lasers-and-energy-based-devices/photobiomodulation. Accessed 15 July 2021.
3. Hamblin, M. R., Huang, Y.-Y., & Heiskanen, V. (2018). Non-mammalian Hosts and Photobiomodulation: Do All Life-forms Respond to Light? Photochemistry and Photobiology. DOI:10.1111/php.12951.
4. Dompe C., Moncrieff L., Matys J., Lesniak K-G., Kocherova I., Bryja A., Photobiomodulation—Underlying Mechanism and Clinical Applications. J Clin Med. 2020 Jun; 9(6): 1724. DOI: https://dx.doi.org/10.3390%2Fjcm9061724
5. Cheng-Yi Liu T., Ling Jiao J., Yang Xu X., Guang Liu X., Xun Deng S., Hao Liu S. Photobiomodulation: phenomenology and its mechanism.Proceedings Volume 5630, Optics in Health Care and Biomedical Optics: Diagnostics and Treatment II; (2005). DOI: https://doi.org/10.1117/12.581165
6. Clinical application of photobiomodulation therapy in a zoological setting. The Veterinary Nurse. Vol.11 No.10. DOI: https://doi.org/10.12968/vetn.2020.11.10.460

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