School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, Wales, UK.
Cardiff Institute for Tissue Engineering and Repair (CITER), Cardiff University, Cardiff CF24 4HQ, Wales, UK.
Int J Mol Sci. 2021 Mar 29;22(7):3525. doi: 10.3390/ijms22073525.
Retinal lipofuscin which accumulates with age in the retinal pigment epithelium (RPE) is subjected to daily exposures to high fluxes of visible light and exhibits potent photosensitising properties; however, the molecules responsible for its photoreactivity remain unknown. Here, we demonstrate that autooxidation of docosahexaenoate (DHE) leads to the formation of products absorbing, in addition to UVB and UVA light, also visible light. The products of DHE oxidation exhibit potent photosensitising properties similar to photosensitising properties of lipofuscin, including generation of an excited triplet state with similar characteristics as the lipofuscin triplet state, and photosensitised formation of singlet oxygen and superoxide. The quantum yields of singlet oxygen and superoxide generation by oxidised DHE photoexcited with visible light are 2.4- and 3.6-fold higher, respectively, than for lipofuscin, which is consistent with the fact that lipofuscin contains some chromophores which do contribute to the absorption of light but not so much to its photosensitising properties. Importantly, the wavelength dependence of photooxidation induced by DHE oxidation products normalised to equal numbers of incident photons is also similar to that of lipofuscin-it steeply increases with decreasing wavelength. Altogether, our results demonstrate that products of DHE oxidation include potent photosensitiser(s) which are likely to contribute to lipofuscin photoreactivity.
随着年龄的增长，视网膜色素上皮（RPE）中积累的视网膜脂褐素每天都会受到可见光强通量的照射，并表现出很强的光敏特性；然而，导致其光反应性的分子仍然未知。在这里，我们证明二十二碳六烯酸（DHE）的自动氧化导致形成的产物除了吸收 UVB 和 UVA 光之外，还吸收可见光。DHE 氧化产物具有很强的光敏特性，类似于脂褐素的光敏特性，包括生成与脂褐素三重态具有相似特征的激发三重态，以及光敏生成单线态氧和超氧。用可见光激发氧化 DHE 生成单线态氧和超氧的量子产率分别比脂褐素高 2.4 倍和 3.6 倍，这与脂褐素含有一些吸收光但对其光敏特性贡献不大的发色团的事实一致。重要的是，DHE 氧化产物光氧化诱导的归一化为相同入射光子数的波长依赖性也与脂褐素相似——随波长的减小而急剧增加。总之，我们的结果表明，DHE 氧化产物包括可能导致脂褐素光反应性的有效光敏剂。
