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Updated: Apr 11, 2026

Photostimulation by Femtosecond Laser Activates Extracellular-signal-regulated Kinase ERK Signaling or Mitochondrial Events in Target Cells
Published on: July 6, 2019
Molecular pathway of near-infrared laser phototoxicity involves ATF-4 orchestrated ER stress
Imran Khan1, Elieza Tang1, Praveen Arany1
1Cell Regulation and Control Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda MD.
Abstract:
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.
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