Abstract
To better understand the molecular mechanisms responsible for light-induced damage in retinal pigmented epithelial (RPE) cells, we developed an automated device to recapitulate intense light exposure. When compared with human fibroblasts, ARPE-19 cells that had been exposed to blue-rich light-emitting diode-light of 10 000 Lux at 37 °C for 9 h displayed dramatic cellular apoptosis. Collectively, gene expression profiling and qPCR demonstrated that growth arrest and DNA damage-45α (GADD45α) expression was markedly upregulated. Transient knockdown of GADD45α partially attenuated light-damage-induced apoptosis in ARPE-19 cells, whereas GADD45α overexpression dramatically increased it. These results demonstrate the critical function of GADD45α in light-induced RPE cellular apoptosis. Quantitative reverse transcription-PCR and western blotting revealed that the upregulation of GADD45α was under direct control of p53. Moreover, treatment with Ly294002, an inhibitor of AKT phosphorylation, further promoted GADD45α gene transcription in both non-light and light-damaged ARPE-19 cells. Treatment also exacerbated RPE cellular apoptosis after light exposure, confirming that inhibition of Akt phosphorylation increases GADD45α expression. Collectively, our findings reveal that light irrigation induces human RPE cellular apoptosis through upregulation of GADD45α expression mediated through both the p53 and phosphatidylinositol 3-kinase-AKT signaling pathways. These results provide new insights into human retinal diseases elicited by light damage and open a new avenue for disease prevention and treatment.
Highlights
It has long been recognized that excessive light exposure produces photochemical lesions in the retina, leading to the damage of retinal pigmented epithelial (RPE) cells and the neural retina.1,2 Results from previous studies suggest that light-induced RPE damage may be one of the most important factors associated with age-related macular degeneration, solar retinopathy, and other retinal degenerative lesions.3–6 To this end, RPE cells are susceptible to wavelengths within the blue region of the spectrum.7,8 Despite this, many aspects of lightinduced damage to RPE cells remain unclear, with the biological mechanisms behind such damage virtually unknown
Previous studies have focused on how blue light damages RPE cells, the effect of light-emitting diodes (LEDs) on the retina still requires much work, with particular focus needed for the molecular mechanisms behind such damage
Using this in vitro surrogate, we found serious RPE cellular apoptosis resulting from extensive exposure to blue-intensive LED light
Summary
It has long been recognized that excessive light exposure produces photochemical lesions in the retina, leading to the damage of retinal pigmented epithelial (RPE) cells and the neural retina. Results from previous studies suggest that light-induced RPE damage may be one of the most important factors associated with age-related macular degeneration, solar retinopathy, and other retinal degenerative lesions. To this end, RPE cells are susceptible to wavelengths within the blue region of the spectrum. Despite this, many aspects of lightinduced damage to RPE cells remain unclear, with the biological mechanisms behind such damage virtually unknown. Results from previous studies suggest that light-induced RPE damage may be one of the most important factors associated with age-related macular degeneration, solar retinopathy, and other retinal degenerative lesions.. Results from previous studies suggest that light-induced RPE damage may be one of the most important factors associated with age-related macular degeneration, solar retinopathy, and other retinal degenerative lesions.3–6 To this end, RPE cells are susceptible to wavelengths within the blue region of the spectrum.. Light pollution has become increasingly more common with the advent of new technologies and devices in domestic lighting, which has drawn the attention of researchers in the retinal degeneration field.. We have developed an instrument with controllable light intensity and temperature to imitate lightinduced apoptosis on RPE cells Using this in vitro surrogate, we found serious RPE cellular apoptosis resulting from extensive exposure to blue-intensive LED light. Our research offers a novel target for light-induced visual impairment
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