June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
3D-Bioprinted Outer Blood Retinal Barrier Model to Characterize the Role of Senescent Fibroblasts in Driving RPE Dysfunction
Amir Ali; Eric Nguyen; Rishabh Hirday; Russell Quinn; Devika Bose; Minhye Kwak; Jair Montford; Tea Soon Park; Ruchi Sharma; Kapil Bharti
Author Affiliations & Notes
  • Amir Ali
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
    School of Medicine, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Eric Nguyen
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Rishabh Hirday
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Russell Quinn
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Devika Bose
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Minhye Kwak
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Jair Montford
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Tea Soon Park
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Ruchi Sharma
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Kapil Bharti
    Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health Clinical Center, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Amir Ali None; Eric Nguyen None; Rishabh Hirday None; Russell Quinn None; Devika Bose None; Minhye Kwak None; Jair Montford None; Tea Soon Park None; Ruchi Sharma None; Kapil Bharti None
  • Footnotes
    Support  NEI IRP grant ZIA EY000532-08, NEI IRP Grant ZIA EY000542-07, NEI IRP Grant ZIA EY000533-08, Bright Focus Foundation Grant M2020258
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3154 – F0428. doi:
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      Amir Ali, Eric Nguyen, Rishabh Hirday, Russell Quinn, Devika Bose, Minhye Kwak, Jair Montford, Tea Soon Park, Ruchi Sharma, Kapil Bharti; 3D-Bioprinted Outer Blood Retinal Barrier Model to Characterize the Role of Senescent Fibroblasts in Driving RPE Dysfunction. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3154 – F0428.

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Abstract

Purpose : Chronic inflammation and tissue senescence have been implicated in the onset of dry age-related macular degeneration (AMD), but the role of choroidal fibroblasts in AMD pathogenesis is not well understood. To better understand the role of choroidal fibroblasts in AMD pathogenesis, we established an in vitro 3D bioprinted outer blood-retinal barrier (oBRB) model utilizing either iPSC fibroblasts or senescent adult fibroblasts and analyzed their effects on choroidal maturation and RPE functionality.

Methods : A 3D bioprinting system generated a model choroid tissue consisting of pericytes, endothelial cells (EC), and either iPSC-derived or senescent fibroblasts deposited on a PET transwell membrane. After 1 week of maturation, an iPSC-derived RPE monolayer was deposited on the opposite side of the PET membrane to complete the oBRB model. After 4 further weeks of maturation, the effects of iPSC-derived or senescent fibroblasts were evaluated using vasculature network area, transepithelial resistance (TER), PLVAP expression and Luminex analysis for tissue cytokine secretions in media. Two-way ANOVA and Tukey’s Multiple Comparisons Test were utilized for analysis.

Results : Vasculature network area was significantly increased in iPSC versus senescent fibroblast tissues (P≤0.0001). Senescent fibroblasts increased PLVAP/GFP Colocalization in EC, indicating increased potential for fenestration formation in EC. TER values in RPE were significantly increased in iPSC vs. senescent tissues (p≤0.0001). The inclusion of senescent fibroblasts in tissues caused a significant increase in IL-1B, IL6 and IL8 in media.

Conclusions : Senescent choroidal fibroblast tissues have decreased choriocapillaris development and worsened RPE maturation and functionality compared to iPSC-derived tissues. Our work indicates a critical role of fibroblasts in RPE and choriocapillaris degeneration and in inflammatory processes associated with AMD pathogenesis.

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

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Copyright © 2025 Association for Research in Vision and Ophthalmology.
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