Adaptive optics reveals stability of cellular mosaicism in the eye
Heterogeneity of cells of the same type within a given tissue is well documented. However, as imaging individual cells in the same tissue over time is a challenge, little is known about the relevance of this variation for health and in disease. In this episode, Johnny Tam and colleagues use adaptive optics fluorescence microscopy to longitudinally evaluate mosaicism of retinal pigment epithelial (RPE) cells directly in the human eye. Patterns of cell mosaicism in the RPE were stable over time in healthy subjects; however, patterns were not stable over time in a subject with Bietti crystalline dystrophy. These results demonstrate that within the eye patterns of heterogeneity have long-term stability but these patterns can be disrupted in disease.
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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.
Authors
HaeWon Jung, Jianfei Liu, Tao Liu, Aman George, Margery G. Smelkinson, Sarah Cohen, Ruchi Sharma, Owen Schwartz, Arvydas Maminishkis, Kapil Bharti, Catherine Cukras, Laryssa A. Huryn, Brian P. Brooks, Robert Fariss, Johnny Tam
