Mechanisms of Action of Red Light Therapy(PBMT)(1)

Red light Therapy(PBM) is very different from the conventional use of photon energy in laser medicine where heating and burning are the prevailing mechanisms of action. Instead of relying on thermal activity, this new light therapy approach exploits the photochemical conversion potential of low-intensity FR/NIR (630-1000 nm) light.

The first insights into the mechanism of PBM came from studies in the late 1980s and 1990s that implicated mitochondria as the subcellular targets of FR/NIR^[24]–^[27]. It was proposed by Karu^[28] that cytochrome C oxidase inside mitochondria serves as the primary photoacceptor. Cytochrome C oxidase is the enzyme that catalyzes the transfer of electrons from cytochrome C to molecular oxygen-the final step in the mitochondrial respiratory chain and essential for the sustained availability of energy inside cells. Further studies of the action spectrum of the FR/NIR light (defined as the biological response as a function of wavelength) also pointed towards cytochrome C oxidase as the main photoacceptor mediator^[29]–^[30]. Research in cell culture using HeLa cells^[30]–^[31], and primary neurons^[32], demonstrated directly that PBM enhances the activity of cytochrome C oxidase. For instance, Wong-Riley et al^[32] showed that 670 nm light completely reverses the ability of tetrodotoxin, which is a sodium channel blocker capable of indirect down-regulation of cytochrome C oxidase, to diminish this enzyme's activity in primary cultured neuronal cells. Also, PBM competed with potassium cyanide-an irreversible inhibitor of cytochrome C oxidase such that PBM's effectiveness to protect neurons from dying decreased with the increase of the potassium cyanide concentration. The hypothesis of cytochrome C oxidase being the primary target and effector of PBM is further supported by Eells et al's^[33] discovery that NIR light reverses the inhibitory and toxic effect of formic acid (the active metabolite in methanol intoxication), on mitochondrial cytochrome C oxidase in rat retinas, resulting in improved vision outcomes. The stimulation of cytochrome C oxidase by FR/NIR light is believed to lead to an increase in the energy production by mitochondria, increase in the metabolic rate, in cell proliferation and migration^[6],^[34].

Further, in vivo studies using retinas from diabetic rats demonstrated that PBM leads to decrease in diabetes-induced inflammation or retinal vessels^[35]. A cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated with red light showed that PBM causes marked changes in gene expression, including an upregulation in the proteins that comprise the mitochondrial respiratory chain and anti-oxidant genes^[36]. At the same time, PBM was shown to cause a downregulation of genes implicated in apoptosis and the stress response.

Excerpted from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768515/