Abstract
Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-κB (NFκB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Muller glial cells, spanning the entirety of the retina, are involved in DR inflammation. Mitigation of DR pathology currently occurs via invasive, frequently ineffective therapies which can cause adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will diminish oxidative stress preventing downstream inflammatory mechanisms associated with DR initiated by Muller cells. In this study, we used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm2) or no light (sham) daily. We report that a single 670 nm light treatment diminished reactive oxygen species (ROS) production and preserved mitochondrial integrity in this in vitro model of early DR. Furthermore, treatment for 3 days in culture reduced NFκB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this in vitro high glucose model system suggests light treatment could mitigate early deleterious effects modulating inflammatory signaling and diminishing oxidative stress.
Highlights
Examination of the effects of 670nm light treatment on signaling pathways that are activated in response to cell exposure to high glucose were performed in an immortalized rat Muller glial cell line
Increasing intracellular reactive oxygen species (ROS) activates nuclear factor-κB (NFκB) and other pathogenic mechanisms leading to diabetic retinopathy
Bar graph representing rMC-1 cells were cultured in either normal glucose or high glucose medium for 72 hours. 670nm or sham control was applied to the cells at 4.5 J/cm2 daily while in culture. (A) vascular endothelial growth factor (VEGF) mRNA was analyzed via qPCR and normalized to actin. mRNA levels were calculated by ΔΔCt and normalized to Normal glucose sham
Summary
670nm photobiomodulation modulates Muller cells challenged with high glucose healthsciences/). The authors wish to thank Quantum Devices Inc. (Barneveld, WI) for providing the LED arrays used in these studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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