Exposure to Optogenetic Blue Light Attenuates Inflammatory Gene Expression in Non‐transgenic Murine Microglia

Abstract

The prevalence of fluorescent assisted studies and assays together with the advent of optogenetics have led to a dramatic increase in the use of blue light on living tissues both in vitro and in vivo. However, the potential effects of blue light on the behavior of cells not expressing optogenetic proteins has been little reported. Here we studied the effect of repetitive low-level blue light (450nm) exposure on immortalized and primary murine microglial gene expression via qRT-PCR. The inflammatory activities of microglia, CNS resident immune cells, are implicated in most neurodegenerative and traumatic disorders, thus the response of these cells to blue light exposure aimed at modulating the activities of other cells may have clinical importance. We found that blue light altered basal microglial inflammatory and neurotrophic/anti-inflammatory gene expression, effects that were gene- and dose-dependent. Further, blue light delivered in this manner had a potent anti-inflammatory effect on microglial responses to the pro-inflammatory stimulus lipopolysaccharide (LPS). These results demonstrate that long-term optogenetic and fluorescence-based studies in living tissue may have previously unexpected and unreported off-target effects. However, they also suggest an opportunity to consider the use of blue light as a therapeutic agent due to its ability to attenuate microglial pro-inflammatory activities induced by stimuli such as LPS. Studies are currently underway to evaluate the effects of blue light on microglia in vivo. (Supported by the DARPA HIST project and NIH R01 HL111598).