Molecular pathway of near-infrared laser phototoxicity involves ATF-4 orchestrated ER stress

Sci Rep. 2015 Jun 1;5:10581. doi: 10.1038/srep10581.


High power lasers are used extensively in medicine while lower power applications are popular for optical imaging, optogenetics, skin rejuvenation and a therapeutic modality termed photobiomodulation (PBM). This study addresses the therapeutic dose limits, biological safety and molecular pathway of near-infrared (NIR) laser phototoxicity. Increased erythema and tissue damage were noted in mice skin and cytotoxicity in cell cultures at phototoxic laser doses involving generation of reactive oxygen species (ROS) coupled with a rise in surface temperature (>45 °C). NIR laser phototoxicity results from Activating Transcription Factor-4 (ATF-4) mediated endoplasmic reticulum stress and autophagy. Neutralizations of heat or ROS and overexpressing ATF-4 were noted to rescue NIR laser phototoxicity. Further, NIR laser mediated phototoxicity was noted to be non-genotoxic and non-mutagenic. This study outlines the mechanism of NIR laser phototoxicity and the utility of monitoring surface temperature and ATF4 expression as potential biomarkers to develop safe and effective clinical applications.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Activating Transcription Factor 4 / metabolism*
  • Animals
  • Apoptosis
  • Cell Line
  • DNA Damage / radiation effects
  • Endoplasmic Reticulum Stress*
  • Hot Temperature
  • Humans
  • Lasers / adverse effects*
  • Mice
  • Reactive Oxygen Species / metabolism
  • Reproducibility of Results
  • Signal Transduction / radiation effects*
  • Skin / metabolism
  • Skin / radiation effects
  • Skin Temperature / radiation effects


  • Reactive Oxygen Species
  • Activating Transcription Factor 4