Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

TLDR

Photobiomodulation (PBM), also called low‑level light therapy, has been studied for almost 50 years yet remains controversial because its molecular mechanisms are poorly understood, with cytochrome c oxidase identified as a key near‑infrared chromophore. This review summarizes recent advances that clarify PBM’s cellular and molecular actions. The prevailing model proposes that photons release nitric oxide from cytochrome c oxidase, boosting electron transport, mitochondrial membrane potential and ATP, while light‑activated ion channels permit calcium influx and downstream ROS, cAMP, NO and Ca²⁺ signaling that activate transcription factors. Activation of these transcription factors upregulates genes for protein synthesis, cell migration, proliferation, anti‑inflammatory, anti‑apoptotic, and antioxidant responses, with stem and progenitor cells showing heightened sensitivity to LLLT.

Abstract

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.