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ResearchIn-Press PreviewCell biologyOphthalmology Open Access | 10.1172/JCI198648

Retinol tracing within murine neural retina reveals cell type-specific retinol transport and distribution

Zachary J. Engfer,1 Grazyna Palczewska,1 Samuel W. Du,1 Jianye Zhang,1 Zhiqian Dong,1 Carolline Rodrigues Menezes,1 Jun Wang,2 Jianming Shao,2 Budd A. Tucker,3 Robert F. Mullins,3 Rui Chen,1 Philip D. Kiser,1 and Krzysztof Palczewski1

1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

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1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

Find articles by Chen, R. in: PubMed | Google Scholar |

1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

Find articles by Kiser, P. in: PubMed | Google Scholar |

1Brunson Center for Translational Vision Research, Department of Ophthalmolo, University of California, Irvine, United States of America

2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States of America

3Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, United States of America

Find articles by Palczewski, K. in: PubMed | Google Scholar |

Published November 18, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI198648.
Copyright © 2025, Engfer et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 18, 2025 - Version history
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Abstract

11-cis-Retinal is essential for light perception in mammalian photoreceptors (PRs), and aberrations in retinoid transformations cause severe retinal diseases. Understanding these processes is crucial for combating blinding diseases. The visual cycle, operating within PRs and the retinal pigment epithelium (RPE), regenerates 11-cis-retinal to sustain light sensitivity. Retinoids are also present in Müller glia (MG), hypothesized to supply 11-cis-retinol to cone PRs and retinal ganglion cells (RGCs). To trace retinoid movement through retinal cell types, we used cell-specific knock-in of lecithin:retinol acyltransferase (LRAT), which converts retinols into stable retinyl esters (REs). Ectopic LRAT expression in murine PRs, MG, and RGCs resulted in RE synthesis, with REs differing in abundance and isomeric composition across cell types under genetic and light-based perturbations. PR inner segments showed high 11-cis-RE content, suggesting a constant 11-cis-retinoid supply for pigment regeneration. In MG expressing LRAT, all-trans-REs were detected, contrasting with 11-cis-REs in PRs. The MG-specific LRAT phenotype mirrored the RE-rich human neural retina, suggesting human MG may utilize LRAT to maintain retinoid reservoirs. Our findings reveal tightly controlled retinoid flux throughout the mammalian retina supporting sustained vision, expanding understanding of the visual cycle to combat retinal diseases.

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graphical abstract
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Version history
  • Version 1 (November 18, 2025): In-Press Preview
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