Journal article
Retinol tracing within murine neural retina reveals cell type-specific retinol transport and distribution
The Journal of clinical investigation, Vol.136(3), e198648
02/02/2026
DOI: 10.1172/JCI198648
PMCID: PMC12867154
PMID: 41252217
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.
Details
- Title: Subtitle
- Retinol tracing within murine neural retina reveals cell type-specific retinol transport and distribution
- Creators
- Zachary J Engfer - University of California, IrvineGrazyna Palczewska - University of California, IrvineSamuel W Du - University of California, IrvineJianye Zhang - University of California, IrvineZhiqian Dong - University of California, IrvineCarolline Rodrigues Menezes - University of California, IrvineJun Wang - Baylor College of MedicineJianming Shao - Baylor College of MedicineBudd A Tucker - University of IowaRobert F Mullins - University of IowaRui Chen - University of California, IrvinePhilip D Kiser - University of California, IrvineKrzysztof Palczewski - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.136(3), e198648
- DOI
- 10.1172/JCI198648
- PMID
- 41252217
- PMCID
- PMC12867154
- NLM abbreviation
- J Clin Invest
- ISSN
- 1558-8238
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Grant note
- National Eye Institute, NIH: R01EY029750, EY035889, EY032104, R01EY034123 Prevent Blindness Inc. Special Scholar Award Norman Raab Foundation Wilmer Eye Institute Johns Hopkins School of Medicine. Branna and Irving Sisenwein Professorship in Ophthalmology
This work is the result of NIH funding, in whole or in part, and is subject to the NIH Public Access Policy. Through acceptance of this federal funding, the NIH has been given a right to make the work publicly available in PubMed Central.center dot National Eye Institute, NIH grants R01EY029750, EY035889, and EY032104 to AS and R01EY034123 to AM.center dot Research to Prevent Blindness Inc. Special Scholar Award to AS.center dot Unrestricted grants to the Wilmer Eye Institute, Johns Hopkins School of Medicine.center dot Norman Raab Foundation to AS. Branna and Irving Sisenwein Professorship in Ophthalmology to AS.
- Language
- English
- Electronic publication date
- 11/18/2025
- Date published
- 02/02/2026
- Academic Unit
- The University of Iowa Institute for Vision Research; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9985033761302771
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