Language
English
Publication Date
11-18-2025
Journal
The Journal of Clinical Investigation
DOI
10.1172/JCI198648
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.
Keywords
Cell biology, Ophthalmology, Retinopathy
Published Open-Access
yes
Recommended Citation
Engfer, Zachary J; Palczewska, Grazyna; Du, Samuel W; et al., "Retinol Tracing Within Murine Neural Retina Reveals Cell Type-Specific Retinol Transport and Distribution" (2025). Faculty, Staff and Students Publications. 6435.
https://digitalcommons.library.tmc.edu/baylor_docs/6435