Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

Lucas Freitas De Freitas, Michael R. Hamblin

Research output: Contribution to journalArticlepeer-review

867 Citations (Scopus)


Photobiomodulation 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-infrared 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 adenosine triphosphate production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium (Ca2+) 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, and antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.

Original languageEnglish
Article number7488285
Pages (from-to)348-364
Number of pages17
JournalIEEE Journal of Selected Topics in Quantum Electronics
Issue number3
Publication statusPublished - 1 May 2016
Externally publishedYes


  • Light sensitive ion channels
  • Low level light therapy
  • Photobiomodulation
  • cytochrome c oxidase (Cox)
  • mechanism
  • mitochondria

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Electrical and Electronic Engineering


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