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Marie-Christine Lambert, Mathieu Ouellette, Elodie Boisselier, Patrick J Rochette; Photo-conversion of A2E by high-energy visible light. Invest. Ophthalmol. Vis. Sci. 2018;59(9):363.
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Lipofuscin accumulation in the retina is a major risk factor of age-related macular degeneration (AMD). A2E, the main component of lipofuscin, is produced in the outer segment of photoreceptors and accumulates in retinal pigmented epithelial (RPE) cells after phagocytosis of photoreceptors outer segments. Accumulation of A2E is toxic for RPE cells and can lead to their death. The absorption spectrum of A2E, which peaks around 435 nm, absorbs the high-energy visible blue light (HEV). The absorption of high doses of HEV light by high concentration of A2E leads to the formation of reactive oxygen species (ROS) that could cause RPE cell death, which eventually plays a role in the development of AMD. Preliminary data in our lab show that, at physiological HEV light doses, A2E is converted to non-HEV light absorbing products. In this project, we have determined parameters of photo-conversion of A2E. We have evaluated the influence of irradiation surface, concentration of A2E and total volume in A2E photo-conversion.
A2E, diluted in DMSO, was irradiated with 0 to 1000 kJ/m2 HEV light. The UV-visible spectrum of the irradiated A2E was measured and the absorption values between 435 and 445 nm was used to compare the different conditions and determine photo-conversion curves of A2E. Different experiments were performed using this irradiation protocol. (1) Antioxidants were added to A2E before the irradiation to determine the implication of oxidation in the photo-conversion of A2E. (2) Chronic irradiation with low doses of HEV light was used to determine the impact of the irradiation regimen. (3) We modified A2E concentration, volume, temperature and surface of irradiation to determine whether they can affect A2E photo-conversion.
Antioxidants did not affect the rate of A2E photo-conversion, suggesting that the photo-conversion is oxidation-independent. We found that the rate of A2E photo-conversion is not influenced by the irradiation regimen (chronic vs acute) but is greatly modified by A2E concentration and volume. Those results suggest that the cumulative photon energy of HEV per mole of A2E is the main factor driving A2E photo-conversion.
This project shed light on the potential factors influencing the photo-conversion of A2E by HEV light. The following step of the project would be to identify the photo-conversion products of A2E and their toxicity for RPE cells.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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