Blue Light Excited Retinal Disrupts Cellular Signaling

by | Aug 5, 2019 | 2018, Eye Health, Vitamin A

Written by Angeline A. De Leon, Staff Writer. This study demonstrates how retinal-generated toxicity by blue light irreversibly damages retinal cells of the eye which may contribute to earlier onset of age-related macular degeneration.

eye healthRetinal is a photosensitive derivative of vitamin A and plays a role in the transduction of light into neural signals associated with vision 1,2. A specific type of retinal, 11-cis retinal (11CR), acts as the light-sensing chromophore (molecule responsible for coloring of compounds) in visual pigments, and disruption of 11CR regeneration leads to accumulation of another form of retinal, all-trans retinal (ATR, a potent photosensitizer known to induce oxidation of proteins and lipids in the photoreceptor membrane) 3-5. Animal studies link ATR accumulation to age-related macular degeneration, acute light-induced retinopathy, and night blindness 6. Photooxidation of ATR is associated with reactive oxygen species (ROS) generation, leading to cytotoxicity and apoptosis (cell death) 7,8 through a process that scientists hypothesize involve activation of G-protein coupled receptors (GPCRs, membrane receptors involved in the mediation of vision) 9. In a 2018 study 10 conducted by investigators at the University of Toledo, researchers examined the cellular effects associated with blue light’s photosensitization of free retinal in cells, specifically looking at potential signaling disruptions (particularly involving biphosphate, PIP2, a key regulator of various cellular functions) induced by photoexcited retinal in living cells.

HeLa (an immortal cell line) cells were cultured, and live cell imaging experiments performed to examine photoactivation in regions of interest in cells. Cell cultures were checked for PIP2 sensor expression, and calcium (linked to cytotoxicity in retina) imaging was performed using a fluorescent calcium indicator. To assess cytotoxicity of cells, HeLa cells were imaged following exposure to either blue light only (4.86 µW of 445 nm wavelength), ATR only (concentration of 50 µm), or blue light in the presence of ATR.  To analyze retinal degradation, an ATR solution was separately exposed to blue light emitting diodes (LED) and white fluorescent light continuously up to 30 minutes, and percent retinal content in each sample was calculated.

Results indicated that following exposure to low intensity blue light, cells exhibited PIP2 hydrolysis and translocation of PIP2 sensor to the cytosol, indicative of a disruption in normal PIP2 signaling by blue light excited retinal. When exposed to blue light, 11CR also exhibited PIP2 disruption. Blue light excited retinal induced PIP2 distortion was found to be independent of GPCR-G protein activation. Time-lapse microscopy looking at the morphology of HeLa cells incubated in retinal containing medium showed substantial morphological changes only in cells exposed to blue light, such as protrusion of the plasma membrane of cells. Select cells exposed to blue light in the presence of retinal also showed incorporation of propidium iodide, a cell-death marker, suggesting that prolonged exposure of cells to blue light excited retinal is associated with cell death. Significant retinal degradation was also observed when a solution of ATR was exposed to blue LED light for half an hour. Finally, compared to control cells, hypoxic cells (deprived of oxygen) showed reduced PIP2 sensor translocation upon exposure to blue light excited retinal, confirming that PIP2 distortion is associated with ROS mechanisms. When, prior to blue light exposure, cells were incubated with antioxidants (water-soluble glutathione and lipid-soluble alpha-tocopherol), only cells incubated with alpha-tocopherol showed attenuated PIP2 sensor translocation, suggesting that oxidative damage induced by blue light excited retinal likely occurs in the lipid membrane of cells.

General results of the study suggest that by altering normal PIP2 signaling, blue light excited retinal exerts significant influence over cellular physiology of photoreceptor cells. Results suggest that perturbation of PIP2 signaling is independent of GPCR activation and that disrupted cellular signaling is characterized by changes in cell morphology and markers of cytotoxicity. Researchers suggest that photoexcited retinal-induced PIP2 disturbance may be linked to ROS mechanisms taking place within the plasma membrane. Findings speak to the potential health risks associated with blue light exposure at the cellular level and more specifically, the widespread impact of blue light induced PIP2 distortion in photoreceptor cells.

Source: Ratnayake K, Payton JL, Lakmal H, et al. Blue light excited retinal intercepts cellular signaling. Scientific Reports. 2018; 8: 10207. DOI: 10.1038/s41598-018-28254-8.

© The Author(s) 2018. Licensed under a Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/.

Posted August 5, 2019.

Click here to read the full text study.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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