The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones.
The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones.
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DOI：
10.1017/s0952523817000013
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发表时间：
2017-01
影响因子：
1.9
通讯作者：
Kefalov VJ
中科院分区：
文献类型：
--
作者：
Sato S;Frederiksen R;Cornwall MC;Kefalov VJ
脊椎动物的视杆细胞和视锥细胞需要持续的发色团供应，以便在光活化后再生它们的视色素。介导我们白天视觉的视锥细胞需要特别快速地供应11-顺式视网膜发色团，以维持它们在强光下的功能。对这一过程的重要贡献被认为是发色团前体11-顺式视黄醇，其从视网膜中的米勒细胞供应到视锥细胞，随后氧化为11-顺式视黄醇作为视网膜视觉周期的一部分。然而，视锥细胞中的顺式视黄醇氧化酶的分子身份仍不清楚。在这里，作为表征这种酶促反应的第一步，我们试图确定这种活性在蝾螈红锥中的亚细胞定位。我们发现，孤立的蝾螈红锥暗适应的发病速度大大加快时，直接暴露其外部与其内部段9-顺式视黄醇，11-顺式视黄醇的类似物。相比之下，当用9-顺式视黄醛（一种可直接支持色素再生的发色团类似物）处理外节与内节时，未观察到这种差异。这些结果表明，令人惊讶的是，顺式视黄醇氧化发生在锥体光感受器的外节。重申这一观点，色素再生与外源性添加9-顺式视黄醇直接观察到截短的外节的视锥细胞，但不是在杆。我们的结论是，酶机制所需的氧化回收顺式视黄醇的视网膜视觉周期的一部分是存在于外段的锥。
Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones.