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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E.
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Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E.

机译：Rpe65 Leu450Met变体与视网膜色素上皮脂褐素荧光素A2E和iso-A2E的水平降低有关。

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摘要

There is a growing body of evidence that the nondegradable fluorophores that accumulate as the lipofuscin of retinal pigment epithelium (RPE) are involved in mechanisms leading to the degeneration of RPE in macular degeneration. Most of the constituents of RPE lipofuscin are inadvertent products of the retinoid visual cycle, the enzymatic pathway by which the 11-cis-retinal chromophore of rhodopsin is generated. Indeed, a major constituent of RPE lipofuscin, the pyridinium bisretinoid A2E, is a diretinal conjugate that forms in photoreceptor cells and is deposited in RPE cells as a consequence of the phagocytosis of the outer segment membrane by RPE cells. Given the adverse effects of A2E, there is considerable interest in combating its deposition so as to protect against vision loss. These efforts, however, necessitate an understanding of factors that modulate its formation. Here we show that an amino acid variant in murine Rpe65, a visual-cycle protein required for the regeneration of 11-cis-retinal,is associated with reduced A2E accumulation.
机译：越来越多的证据表明，作为视网膜色素上皮（RPE）的脂褐素积聚的不可降解的荧光团与导致黄斑变性中RPE变性的机制有关。 RPE脂褐素的大多数成分是类视色素视周期的无意产物，视紫红质视周期是视紫红质11-顺-视网膜生色团的酶促途径。实际上，RPE脂褐素的主要成分，吡啶鎓双维甲酸A2E，是一种双视网膜共轭物，它形成在感光细胞中，并由于RPE细胞吞噬外段膜而沉积在RPE细胞中。鉴于A2E的不利影响，人们非常有兴趣对抗其沉积，以防止视力丧失。然而，这些努力需要了解调节其形成的因素。在这里我们显示，鼠Rpe65中的氨基酸变体是11-顺式-视网膜再生所需的视觉循环蛋白，与减少的A2E积累相关。

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