Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal condensation products in mouse eyes

Grazyna Palczewska, Tadao Maeda, Yoshikazu Imanishi, Wenyu Sun, Yu Chen, David R. Williams, David W. Piston, Akiko Maeda, Krzysztof Palczewski

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1444-1450
Number of pages7
JournalNature medicine
Volume16
Issue number12
DOIs
StatePublished - Dec 2010

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