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JCI Insight. 2019 Mar 21;4(6). pii: 124904. doi: 10.1172/jci.insight.124904. eCollection 2019 Mar 21.

Longitudinal adaptive optics fluorescence microscopy reveals cellular mosaicism in patients.

Author information

1
National Eye Institute, NIH, Bethesda, Maryland, USA.
2
National Institute of Allergy and Infectious Disease, Research Technologies Branch, NIH, Bethesda, Maryland, USA.
3
University of North Carolina - Chapel Hill, Chapel Hill, North Carolina, USA.

Abstract

The heterogeneity of individual cells in a tissue has been well characterized, largely using ex vivo approaches that do not permit longitudinal assessments of the same tissue over long periods of time. We demonstrate a potentially novel application of adaptive optics fluorescence microscopy to visualize and track the in situ mosaicism of retinal pigment epithelial (RPE) cells directly in the human eye. After a short, dynamic period during which RPE cells take up i.v.-administered indocyanine green (ICG) dye, we observed a remarkably stable heterogeneity in the fluorescent pattern that gradually disappeared over a period of days. This pattern could be robustly reproduced with a new injection and follow-up imaging in the same eye out to at least 12 months, which enabled longitudinal tracking of RPE cells. Investigation of ICG uptake in primary human RPE cells and in a mouse model of ICG uptake alongside human imaging corroborated our findings that the observed mosaicism is an intrinsic property of the RPE tissue. We demonstrate a potentially novel application of fluorescence microscopy to detect subclinical changes to the RPE, a technical advance that has direct implications for improving our understanding of diseases such as oculocutaneous albinism, late-onset retinal degeneration, and Bietti crystalline dystrophy.

KEYWORDS:

Clinical practice; Genetic diseases; Neuroimaging; Ophthalmology

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