June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Immuno Tomography (IT) and Imaging Mass Cytometry (IMC) for Constructing Spatially Resolved, Multiplexed 3D-IMC Data Sets of the Meibomian gland
Author Affiliations & Notes
  • Donald Brown
    University of California Irvine, University of California Irvine, Irvine, CA, US, academic, Irvine, California, United States
  • Ladan Gheiratmand
    Fluidigm Canada Inc, Markham, Ontario, Canada
  • Daaf Sandkuijl
    Fluidigm Canada Inc, Markham, Ontario, Canada
  • Alexander Loboda
    Fluidigm Canada Inc, Markham, Ontario, Canada
  • James V Jester
    University of California Irvine, University of California Irvine, Irvine, CA, US, academic, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Donald Brown None; Ladan Gheiratmand digm Canada Inc, Code E (Employment); Daaf Sandkuijl digm Canada Inc, Code E (Employment); Alexander Loboda digm Canada Inc, Code E (Employment); James Jester None
  • Footnotes
    Support  NIH/NEI EY021510, an Unrestricted Grant from Research to Prevent Blindness, Inc. RPB-203478, and the Skirball program in Molecular Ophthalmology
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1968 – A0298. doi:
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      Donald Brown, Ladan Gheiratmand, Daaf Sandkuijl, Alexander Loboda, James V Jester; Immuno Tomography (IT) and Imaging Mass Cytometry (IMC) for Constructing Spatially Resolved, Multiplexed 3D-IMC Data Sets of the Meibomian gland. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1968 – A0298.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose :
We have previously used Immuno Tomography (IT) to identify label retaining stem cell populations in the cornea and meibomian gland. While this method provides the unique ability to quantify stem cell populations comprised of 1-4 cells, the number of antigens that can be sequentially used to characterize these unique cells is limited by the antigen stability after antibody stripping and re-probing. To address this deficiency, we have evaluated the capability of imaging mass cytometry (IMC) to generate multiplexed images using metal-conjugated antibodies to label IT plastic sections and generate 3-dimensional IMC data sets (3D-IMC).

Methods :
K5-H2B-GFP mice, 56 days after doxycycline chase were sacrificed and eyelid tissue processed for IT. A total of 400 serial, plastic sections, 2 mm thick were then probed using metal tagged antibodies specific for sox9, collagen type I, E-cadherin, Ki67, GFP, aSMA, vimentin and DNA Intercalator. Multiplexed images were then generated using an Imaging Mass Cytometery system (Fluidigm), and 3D reconstructions assembled.

Results :
All 8 metal labeled tags were detected and their images were successfully assembled into 3D-IMC data sets. GFP labeled nuclei were identified within the meibomian glands in comparable numbers to those previously reported for slow cycling, meibomian gland stem cells.

Conclusions : These findings demonstrate that IMC can be used on plastic sections to generate multiplexed, 3D data sets that can be reconstructed to show the spatial localization of meibomian gland stem cells. We propose 3D-IMC might prove valuable in more fully characterizing stem cell populations in different tissues.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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