Pathways and disease-causing alterations in visual chromophore production for vertebrate vision.
Pathways and disease-causing alterations in visual chromophore production for vertebrate vision.
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DOI：
10.1074/jbc.rev120.014405
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Palczewski K
中科院分区：
文献类型：
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作者：
Kiser PD;Palczewski K
我们对世界的所有看法都始于与杆状和锥状光感受器的视觉色素相关的视黄醛发色团的超快顺式到反式光异构化。这些光感受器的持续响应性随后通过将反式类视黄酮转化为11-顺式结构的再生过程得以维持。最近对视网膜g蛋白偶联受体（RGR）的生化和电生理分析表明，即使在明亮的光线条件下，它也能维持感光细胞，特别是视锥细胞的反应性。因此，有两种机制可以完成再异构化：一种涉及已被充分研究的类视黄醇异构酶（RPE65），另一种涉及由RGR介导的光异构酶反应。将全反式视网膜转化为11顺式视网膜的通路受损与轻度至重度视网膜营养不良有关。此外，随着年龄的增长，发色团的再生速度也有所下降。药理学和遗传学两种方法都被用来绕过视觉周期缺陷，从而减轻致盲疾病。基因组编辑技术的快速发展也为各种视网膜疾病的治疗铺平了道路。在这篇综述中，我们提供了视觉周期生物化学的最新进展，然后讨论视觉周期相关疾病和新兴的治疗方法。有希望这些进展将有助于治疗更复杂的眼部疾病，包括年龄相关性黄斑变性（AMD）。
All that we view of the world begins with an ultrafast cis to trans photoisomerization of the retinylidene chromophore associated with the visual pigments of rod and cone photoreceptors. The continual responsiveness of these photoreceptors is then sustained by regeneration processes that convert the trans-retinoid back to an 11-cis configuration. Recent biochemical and electrophysiological analyses of the retinal G-protein-coupled receptor (RGR) suggest that it could sustain the responsiveness of photoreceptor cells, particularly cones, even under bright light conditions. Thus, two mechanisms have evolved to accomplish the reisomerization: one involving the well-studied retinoid isomerase (RPE65) and a second photoisomerase reaction mediated by the RGR. Impairments to the pathways that transform all-trans-retinal back to 11-cis-retinal are associated with mild to severe forms of retinal dystrophy. Moreover, with age there also is a decline in the rate of chromophore regeneration. Both pharmacological and genetic approaches are being used to bypass visual cycle defects and consequently mitigate blinding diseases. Rapid progress in the use of genome editing also is paving the way for the treatment of disparate retinal diseases. In this review, we provide an update on visual cycle biochemistry and then discuss visual-cycle-related diseases and emerging therapeutics for these disorders. There is hope that these advances will be helpful in treating more complex diseases of the eye, including age-related macular degeneration (AMD).