Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal condensation products in mouse eyes
Open accessAbstract
Multiphoton excitation fluorescence microscopy (MPM) can image certain molecular processes in vivo. In the eye, fluorescent retinyl esters in subcellular structures called retinosomes mediate regeneration of the visual chromophore, 11-cis-retinal, by the visual cycle. But harmful fluorescent condensation products of retinoids also occur in the retina. We report that in wild-type mice, excitation with a wavelength of ∼730 nm identified retinosomes in the retinal pigment epithelium, and excitation with a wavelength of ∼910 nm revealed at least one additional retinal fluorophore. The latter fluorescence was absent in eyes of genetically modified mice lacking a functional visual cycle, but accentuated in eyes of older wild-type mice and mice with defective clearance of all-trans-retinal, an intermediate in the visual cycle. MPM, a noninvasive imaging modality that facilitates concurrent monitoring of retinosomes along with potentially harmful products in aging eyes, has the potential to detect early molecular changes due to age-related macular degeneration and other defects in retinoid metabolism.
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The RPE also accumulates retinal condensation products, which can be detected by TPM and monitored independently from other retinoids because of their unique spectral properties.
“The RPE also accumulates other retinoids, including retinal condensation products.314,315 These metabolites also can be detected by TPM, and since they are characterized by unique spectral properties, the intracellular accumulation and distribution of these compounds can be monitored independently from other retinoids”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [313]
Condensation products accumulate most prominently in mice lacking the ABCA4 transporter and retinol dehydrogenase 8.
“These condensation products accumulate most prominently in mice lacking the ABCA4 transporter and retinol dehydrogenase 8 (RDH8)”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [313]
Retinosomes lie close to the RPE plasma membrane and are essential for 11-cis-retinal production.
“Retinosomes are located close to the RPE plasma membrane and are essential components for 11-cis-retinal production.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [313]
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- Authors
- Palczewska, G., Maeda, T., Imanishi, Y., Sun, W., Chen, Y., Williams, D. R., Piston, D. W., Maeda, A., & Palczewski, K.
- Affiliations
- Case Western Reserve University (US)
- Polgenix (United States) (US)
- University of Rochester (US)
- Vanderbilt University (US)
- Corresponding author
- Palczewski, Krzysztof
- ORCID
- Venue
- Nature Medicine
- Published
- 2010-11-14
- Volume
- 16
- Issue
- 12
- Pages
- 1444-1449
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3057900
- OpenAlex
- W2162264610
- Cited by
- 88
- References
- 40
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 11 · 2012: 9
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (K08EY019880, EY-008061, R01EY008061, EY019880, R43EY020715, EY009339, K08EY019031, EY019031, EY020715, P30EY011373, R01EY009339)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- retinoid cycle, retinyl esters, visual cycle, 11-cis-retinal regeneration, retinal pigment epithelium, age-related macular degeneration, vitamin A metabolism, endogenous fluorophores, mouse eye
- MeSH terms
- Retinyl Esters, Animals, Eye, Lipoproteins, Pyridinium Compounds, Retinoids, Retinol-Binding Proteins, Vitamin A, Microscopy, Fluorescence, Multiphoton, Mice, Retinal Pigment Epithelium
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