September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Tissue Engineered Human Blood-Retinal Barrier-on-a-Chip
Author Affiliations & Notes
  • Jun Jeon
    Unit on Ocular Stem Cell and Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Nathan Hotaling
    Unit on Ocular Stem Cell and Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
    Biosystems & Biomaterials Division, National Institute of Standards & Technology, Gaithersburg, Maryland, United States
  • Marjon Zamani
    Unit on Ocular Stem Cell and Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
    Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, United States
  • Roba Dejene
    Section on Epithelial & Retinal Physiology & Disease, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Donald Ingber
    Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, United States
  • Kapil Bharti
    Unit on Ocular Stem Cell and Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
    Section on Epithelial & Retinal Physiology & Disease, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Jun Jeon, None; Nathan Hotaling, None; Marjon Zamani, None; Roba Dejene, None; Donald Ingber, None; Kapil Bharti, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5325. doi:
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    • Get Citation

      Jun Jeon, Nathan Hotaling, Marjon Zamani, Roba Dejene, Donald Ingber, Kapil Bharti; Tissue Engineered Human Blood-Retinal Barrier-on-a-Chip. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5325.

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

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Abstract

Purpose : Recent advancements in the field of microfluidics have provided the means to observe tissue and organ-level behaviors in a controlled biomimetic microenvironment. In this study, we recapitulated the human blood-retinal barrier (BRB) in a microfluidic platform using induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) and endothelial cells (ECs) and compared the functionality of our model to that of a standard Transwell co-culture system.

Methods : The poly(dimethylsiloxame) (PDMS) based microfluidic chip used in the experiment was composed of two vertically-stacked microchannels separated by a porous polyethylene terephthalate membrane. Developmentally guided differentiation protocols were used to generate RPE and ECs from iPSCs. The following assays were performed to characterize the functionality of the co-culture system in the chip: permeability to FITC-dextran, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) secretion, RPE pigmentation, and fluid transport across top and bottom channels.

Results : Donor-matched sets of iPSC-derived RPE cells and ECs were successfully generated and co-cultured in our microfluidic device. The top channel was seeded with RPE cells, and the bottom channel was seeded with ECs. The cells were maintained using tissue-specific culture medium continuously perfused by a peristaltic pump, and different flow rates were given to each cell type to more closely mimic the microenvironment of the BRB. The RPE and EC monolayers demonstrated barrier resistance, secreted cytokines in a polarized fashion, and transported water from top channel towards the bottom channel.

Conclusions : Using microfluidic channels to co-culture RPE cells and ECs, we showed that our chip platform is able to model the human BRB as well as a standard Transwell culturing system. In addition, the unique functions offered by the chip, specifically its ability to quantify in-situ the rate of fluid transport across the BRB model, helps pave the way for developing a model of different ocular diseases on the chip, which can serve as an efficient drug discovery platform in the future.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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