Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

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.

Keywords: Cytochrome c oxidase; Light sensitive ion channels; Low Level Light Therapy; Mechanism; Mitochondria; Photobiomodulation.

Figures

Figure 1

Scheme of mitochondrial retrograde signaling pathways as proposed by Karu. The main pathway is represented by continuous arrows, and the complementary ones are represented by segmented arrows.

Figure 2

All the seven subfamilies of Transient Receptor Potential Channels (TRP).

Figure 3

Overview of the different groups of genes and molecules that have NF-kB response elements. In principle these could be activated by NK-kB signaling pathway triggered by the ROS produced during LLLT

Figure 4

A model of the signaling pathways for LLLT protecting cell from UVB-induced senescence.

Figure 5

Reactive Oxygen Species sensors and signaling