Examining the Role of Cone-expressed RPE65 in Mouse Cone Function

Abstract 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...

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Autores principales:	Alexander V. Kolesnikov, Peter H. Tang, Vladimir J. Kefalov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Mouse Cone Cone Dark Adaptation Human RPE RPE65 Expression RPE65 Protein Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e4f64c14d40407aa7abf37214726453
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spelling	oai:doaj.org-article:9e4f64c14d40407aa7abf372147264532021-12-02T15:07:51ZExamining the Role of Cone-expressed RPE65 in Mouse Cone Function10.1038/s41598-018-32667-w2045-2322https://doaj.org/article/9e4f64c14d40407aa7abf372147264532018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32667-whttps://doaj.org/toc/2045-2322Abstract 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.Alexander V. KolesnikovPeter H. TangVladimir J. KefalovNature PortfolioarticleMouse ConeCone Dark AdaptationHuman RPERPE65 ExpressionRPE65 ProteinMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mouse Cone Cone Dark Adaptation Human RPE RPE65 Expression RPE65 Protein Medicine R Science Q
spellingShingle	Mouse Cone Cone Dark Adaptation Human RPE RPE65 Expression RPE65 Protein Medicine R Science Q Alexander V. Kolesnikov Peter H. Tang Vladimir J. Kefalov Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
description	Abstract 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.
format	article
author	Alexander V. Kolesnikov Peter H. Tang Vladimir J. Kefalov
author_facet	Alexander V. Kolesnikov Peter H. Tang Vladimir J. Kefalov
author_sort	Alexander V. Kolesnikov
title	Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
title_short	Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
title_full	Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
title_fullStr	Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
title_full_unstemmed	Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
title_sort	examining the role of cone-expressed rpe65 in mouse cone function
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9e4f64c14d40407aa7abf37214726453
work_keys_str_mv	AT alexandervkolesnikov examiningtheroleofconeexpressedrpe65inmouseconefunction AT peterhtang examiningtheroleofconeexpressedrpe65inmouseconefunction AT vladimirjkefalov examiningtheroleofconeexpressedrpe65inmouseconefunction
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Examining the Role of Cone-expressed RPE65 in Mouse Cone Function

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