Effects of mild- and moderate-intensity illumination on short-term axial length and choroidal thickness changes in young adults.

PURPOSE: Previous studies have shown that time spent outdoors is protective against myopia development in children. In this study, we examined the effects of 500 and 1000 lux of illumination to the eye on axial length (AL) and choroidal thickness (CT) changes in young adults. METHODS: Fifteen participants (mean age, 21.60 years [2.16]) with a mean refraction of -0.34 D (0.37) were exposed to 500 and 1000 lux of illumination for 120 min in a dark room on two different days, using a pair of light-emitting glasses. Ocular measurements were repeated on an additional day in darkness (~5 lux). Ocular biometrics and CT were measured and analysed in the right eye before the light exposure (0 min), after 30, 60 and 120 min of exposure and 30 min after light offset to measure recovery using the Lenstar biometer and the Cirrus optical coherence tomographer, respectively. RESULTS: Exposure to 500 and 1000 lux of illumination resulted in a significant reduction in AL at 30, 60 and 120 min compared to darkness (AL change at 120 min: darkness, +0.020 mm [0.004]; 500 lux, -0.006 mm [0.004]; 1000 lux, -0.013 mm [0.004]; p < 0.001). Exposure to 500 and 1000 lux caused a significant overall thickening of the subfoveal choroid compared to darkness (CT change across 120 min: darkness, -0.010 mm [0.007]; 500 lux, +0.006 mm [0.005]; 1000 lux, +0.009 mm [0.003], p = 0.02). Ocular changes were not significantly different between the two illumination levels (p > 0.05) and returned to baseline within 30 min of light offset. CONCLUSIONS: Exposure to mild- or moderate-intensity illumination on the eye can induce a significant short-term reduction in AL and an increase in CT in young adults. Future studies on larger cohorts with varying light intensities are needed to better understand the effects of ocular illumination on AL changes in humans.

Phototoxic damage to cone photoreceptors can be independent of the visual pigment: the porphyrin hypothesis.

Lighting is rapidly changing with the introduction of light-emitting diodes (LEDs) in our homes, workplaces, and cities. This evolution of our optical landscape raises major concerns regarding phototoxicity to the retina since light exposure is an identified risk factor for the development of age-related macular degeneration (AMD). In this disease, cone photoreceptors degenerate while the retinal pigment epithelium (RPE) is accumulating lipofuscin containing phototoxic compounds such as A2E. Therefore, it remains unclear if the light-elicited degenerative process is initiated in cones or in the RPE. Using purified cone photoreceptors from pig retina, we here investigated the effect of light on cone survival from 390 to 510 nm in 10 nm steps, plus the 630 nm band. If at a given intensity (0.2 mW/cm²), the most toxic wavelengths are comprised in the visible-to-near-UV range, they shift to blue-violet light (425-445 nm) when exposing cells to a solar source filtered by the eye optics. In contrast to previous rodent studies, this cone photoreceptor phototoxicity is not related to light absorption by the visual pigment. Despite bright flavin autofluorescence of cone inner segment, excitation-emission matrix of this inner segment suggested that cone phototoxicity was instead caused by porphyrin. Toxic light intensities were lower than those previously defined for A2E-loaded RPE cells indicating cones are the first cells at risk for a direct light insult. These results are essential to normative regulations of new lighting but also for the prevention of human retinal pathologies since toxic solar light intensities are encountered even at high latitudes.

Blue-violet light decreases VEGFa production in an in vitro model of AMD.

Blue light is an identified risk factor for age-related macular degeneration (AMD). The production of vascular endothelial growth factor (VEGF), leading to neovascularization, is a major complication of the wet form of this disease. We investigated how blue light affects VEGF expression and secretion using A2E-loaded retinal pigment epithelium (RPE) cells, a cell model of AMD. Incubation of RPE cells with A2E resulted in a significant increase in VEGF mRNA and, intracellular and secreted VEGF protein levels, but not mRNA levels of VEGFR1 or VEGFR2. Blue light exposure of A2E-loaded RPE cells resulted in a decrease in VEGF mRNA and protein levels, but an increase in VEGFR1 levels. The toxicity of 440 nm light on A2E-loaded RPE cells was enhanced by VEGF supplementation. Our results suggest that age-related A2E accumulation may result in VEGF synthesis and release. This synthesis of VEGF, which enhances blue light toxicity for the RPE cells, is itself suppressed by blue light. Anti-VEGF therapy may therefore improve RPE survival in AMD.

Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells.

AIMS: Blue light is an identified risk factor for age-related macular degeneration (AMD). We investigated oxidative stress markers and mitochondrial changes in A2E-loaded retinal pigment epithelium cells under the blue-green part of the solar spectrum that reaches the retina to better understand the mechanisms underlying light-elicited toxicity. RESULTS: Primary retinal pigment epithelium cells were loaded with a retinal photosensitizer, AE2, to mimic aging. Using a custom-made illumination device that delivers 10 nm-wide light bands, we demonstrated that A2E-loaded RPE cells generated high levels of both hydrogen peroxide (H2O2) and superoxide anion (O2•-) when exposed to blue-violet light. In addition, they exhibited perinuclear clustering of mitochondria with a decrease of both their mitochondrial membrane potential and their respiratory activities. The increase of oxidative stress resulted in increased levels of the oxidized form of glutathione and decreased superoxide dismutase (SOD) and catalase activities. Furthermore, mRNA expression levels of the main antioxidant enzymes (SOD2, catalase, and GPX1) also decreased. CONCLUSIONS: Using an innovative illumination device, we measured the precise action spectrum of the oxidative stress mechanisms on A2E-loaded retinal pigment epithelium cells. We defined 415-455 nm blue-violet light, within the solar spectrum reaching the retina, to be the spectral band that generates the highest amount of reactive oxygen species and produces the highest level of mitochondrial dysfunction, explaining its toxic effect. This study further highlights the need to filter these wavelengths from the eyes of AMD patients.

Phototoxic action spectrum on a retinal pigment epithelium model of age-related macular degeneration exposed to sunlight normalized conditions.

Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye.