Vitamin A cycle byproducts explain retinal damage and molecular changes thought to initiate retinal degeneration.
Vitamin A cycle byproducts explain retinal damage and molecular changes thought to initiate retinal degeneration.
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DOI：
10.1242/bio.058600
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发表时间：
2021-11-15
期刊：
影响因子：
2.4
通讯作者：
Washington I
中科院分区：
文献类型：
--
作者：
Zhang D;Mihai DM;Washington I
在最常见的视网膜疾病中，包括 Stargardt 病和年龄相关性黄斑变性 (AMD)，维生素 A 的副产物在维生素 A 循环过程中会在视网膜中异常形成。尽管有证据表明它们具有毒性，但这些维生素 A 循环副产物是否会导致视网膜疾病、是症状、有益还是良性，一直存在争议。我们将代表性的维生素 A 副产物 A2E 输送到大鼠的视网膜，并监测电生理、组织学、蛋白质组和转录组的变化。我们发现，维生素 A 循环副产物本身就足以损伤 RPE、光感受器内节和外节以及外丛状层，导致视网膜下碎片的形成，改变转录和蛋白质合成，并削弱视网膜功能。所提供的数据与维生素 A 循环期间维生素 A 副产物的形成既不是良性也不是有益的理论相一致，但可能足以引起最常见的视网膜疾病。延缓维生素 A 副产物的形成可能会解决多种视网膜疾病的根本原因，从而消除数百万人不可逆转的失明威胁。摘要：在维生素 A 循环过程中，维生素 A 的副产物会在眼睛中形成。使用大鼠模型，我们表明仅副产物就可以解释在人类视网膜疾病前驱期观察到的几种视网膜紊乱。延缓这些副产物的形成可以解决最流行的视网膜疾病的根本原因。
In the most prevalent retinal diseases, including Stargardt disease and age-related macular degeneration (AMD), byproducts of vitamin A form in the retina abnormally during the vitamin A cycle. Despite evidence of their toxicity, whether these vitamin A cycle byproducts contribute to retinal disease, are symptoms, beneficial, or benign has been debated. We delivered a representative vitamin A byproduct, A2E, to the rat's retina and monitored electrophysiological, histological, proteomic, and transcriptomic changes. We show that the vitamin A cycle byproduct is sufficient alone to damage the RPE, photoreceptor inner and outer segments, and the outer plexiform layer, cause the formation of sub-retinal debris, alter transcription and protein synthesis, and diminish retinal function. The presented data are consistent with the theory that the formation of vitamin A byproducts during the vitamin A cycle is neither benign nor beneficial but may be sufficient alone to cause the most prevalent forms of retinal disease. Retarding the formation of vitamin A byproducts could potentially address the root cause of several retinal diseases to eliminate the threat of irreversible blindness for millions of people. Summary: During the vitamin A cycle, byproducts of vitamin A form in the eye. Using a rat model, we show that the byproducts alone can explain several retinal derangements observed in the prodromal phase of human retinal disease. Retarding the formation of these byproducts may address the root cause of the most prevalent retinal diseases.
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影响因子：
4.4
作者：
Curcio CA;Zanzottera EC;Ach T;Balaratnasingam C;Freund KB
通讯作者：
Freund KB
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
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通讯作者：
Hollyfield, JG
影响因子：
4.2
作者：
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通讯作者：
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