Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E
Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E
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DOI：
10.1073/pnas.0403499101
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发表时间：
2004-08-10
影响因子：
11.1
通讯作者：
Sparrow, JR
中科院分区：
文献类型：
--
作者：
Kim, SR;Fishkin, N;Sparrow, JR
越来越多的证据表明，作为视网膜色素上皮（RPE）的脂褐素积累的不可降解的荧光团参与导致黄斑变性中RPE变性的机制。RPE脂褐素的大多数成分是类视色素视觉循环的无意产物，类视色素视觉循环是产生视紫红质的11-顺式-视黄质发色团的酶途径。实际上，RPE脂褐素的主要成分吡啶双视黄酸A2 E是在感光细胞中形成的二视网膜缀合物，并且由于RPE细胞吞噬外节膜而沉积在RPE细胞中。鉴于A2 E的不利影响，人们对对抗其沉积以防止视力丧失有着相当大的兴趣。然而，这些努力需要了解调节其形成的因素。在这里，我们表明，在小鼠Rpe 65，11-顺式-视网膜再生所需的视觉周期蛋白的氨基酸变体，与A2 E积累减少。
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.