Examining the Role of Cone-expressed RPE65 in Mouse Cone Function.
Examining the Role of Cone-expressed RPE65 in Mouse Cone Function.
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DOI：
10.1038/s41598-018-32667-w
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发表时间：
2018-09-21
影响因子：
4.6
通讯作者：
Kefalov VJ
中科院分区：
文献类型：
--
作者：
Kolesnikov AV;Tang PH;Kefalov VJ
有效的发色团供应对于脊椎动物视锥光感受器的连续功能是至关重要的。已经确定，RPE 65将视网膜色素上皮中的全反式-至11-顺式-类维生素A异构化是该过程中的关键反应。RPE 65的突变导致发色团供应中断、视网膜变性和失明。有趣的是，最近发现RPE 65也在包括小鼠和人类在内的几个物种的视锥光感受器中表达。然而，视锥细胞表达的RPE 65的功能作用仍然未知。在这里，我们使用功能的损失和增益方法来研究这个问题。首先，我们比较了来自对照和RPE 65缺陷小鼠的视锥细胞的功能。虽然我们发现RPE 65的缺失部分抑制了视锥细胞暗适应，但对这一结果的解释因色素上皮中RPE 65缺失时发色团缺乏引起的视锥细胞结构和功能异常而变得复杂。作为替代方法，我们产生转基因小鼠以在小鼠视锥细胞中表达人RPE 65，其中RPE 65表达通常限于色素上皮。对照（RPE 65缺陷）和转基因（RPE 65表达）锥的比较显示没有形态或功能的变化，只有轻微的延迟，在黑暗中适应，可能是由RPE 65的类视色素的缓冲。总之，我们的研究结果没有提供任何证据证明RPE 65在小鼠视锥细胞中的功能作用。未来的研究将必须确定视锥细胞表达的RPE 65是否在维持视锥细胞中类维生素A的长期稳态及其功能和存活中发挥作用，特别是在人类中。
Efficient chromophore supply is paramount for the continuous function of vertebrate cone photoreceptors. It is well established that isomerization of all-trans- to 11-cis- retinoid in the retinal pigmented epithelium by RPE65 is a key reaction in this process. Mutations in RPE65 result in a disrupted chromophore supply, retinal degeneration, and blindness. Interestingly, RPE65 has recently been found to also be expressed in cone photoreceptors in several species, including mouse and human. However, the functional role of cone-expressed RPE65 has remained unknown. Here, we used loss and gain of function approaches to investigate this issue. First, we compared the function of cones from control and RPE65-deficient mice. Although we found that deletion of RPE65 partially suppressed cone dark adaptation, the interpretation of this result was complicated by the abnormal cone structure and function caused by the chromophore deficiency in the absence of RPE65 in the pigmented epithelium. As an alternative approach, we generated transgenic mice to express human RPE65 in the cones of mice where RPE65 expression is normally restricted to the pigmented epithelium. Comparison of control (RPE65-deficient) and transgenic (RPE65-expressing) cones revealed no morphological or functional changes, with only a slight delay in dark adaptation, possibly caused by the buffering of retinoids by RPE65. Together, our results do not provide any evidence for a functional role of RPE65 in mouse cones. Future studies will have to determine whether cone-expressed RPE65 plays a role in maintaining the long-term homeostasis of retinoids in cones and their function and survival, particularly in humans.
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视网膜类似（视觉）周期的化学。
影响因子：
62.1
作者：
Kiser, Philip D.;Golczak, Marcin;Palczewski, Krzysztof
通讯作者：
Palczewski, Krzysztof
影响因子：
1.9
作者：
Sato S;Frederiksen R;Cornwall MC;Kefalov VJ
通讯作者：
Kefalov VJ
DOI：
10.1073/pnas.250478897
发表时间：
2000-12-05
影响因子：
11.1
作者：
Calvert, PD;Krasnoperova, NV;Lem, J
通讯作者：
Lem, J
影响因子：
5.5
作者：
Nymark, S;Heikkinen, H;Koskelainen, A
通讯作者：
Koskelainen, A
影响因子：
4.4
作者：
Fan, Jie;Rohrer, Baerbel;Crouch, Rosalie K.
通讯作者：
Crouch, Rosalie K.