April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
3D-Bio-engineering of the Conventional Outflow Tract for High Throughput Glaucoma Drug Screening
Author Affiliations & Notes
  • Cula Dautriche
    Nanobioscience, SUNY-College of NanoScale Science & Engineering, Albany, NY
    ophthalmology, SUNY-Downstate Medical Center, Brooklyn, NY
  • Karen Yud Torrejon
    Nanobioscience, SUNY-College of NanoScale Science & Engineering, Albany, NY
  • Magnus Bergkvist
    Nanobioscience, SUNY-College of NanoScale Science & Engineering, Albany, NY
  • Yubing Xie
    Nanobioscience, SUNY-College of NanoScale Science & Engineering, Albany, NY
  • Susan Sharfstein
    Nanobioscience, SUNY-College of NanoScale Science & Engineering, Albany, NY
  • John Danias
    ophthalmology, SUNY-Downstate Medical Center, Brooklyn, NY
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5659. doi:
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      Cula Dautriche, Karen Yud Torrejon, Magnus Bergkvist, Yubing Xie, Susan Sharfstein, John Danias; 3D-Bio-engineering of the Conventional Outflow Tract for High Throughput Glaucoma Drug Screening. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5659.

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

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Abstract
 
Purpose
 

To engineer an in vitro 3D conventional outflow tract to facilitate better understanding of TM outflow physiology and pathology and more rapid development of trabecular meshwork-targeted therapies.

 
Methods
 

Using photolithography techniques, we engineered porous scaffolds with 12 μm pores by patterning the negative photo-resist, SU-8, to mimic the porous micro-architecture of the juxta- canalicular (JCT) layer of the trabecular meshwork. We next assessed the ability of our engineered scaffold, coated with 1% gelatin or hyaluronic acid-based hydrogels, to support primary human trabecular meshwork cells (HTM) or human Schlemm canal cells (HSC) proliferation, growth and development. We subsequently established a co-culture system (Fig 1A) with the HTM and HSC grown on opposite sides of our engineered scaffold and evaluated whether the co-culture system mimics the porous micro-architecture, morphology, physiology, and outflow functions of the in vivo conventional outflow tract via scanning electron microscopy (SEM) analysis, immunohistochemistry (IHC), perfusion studies to assess outflow facility and drug response studies to IOP lowering agents.

 
Results
 

We have successfully established co-culture of HTM and HSC cells on our engineered scaffold so as to mimic the porous micro-architecture of the conventional outflow tract (Fig 1B) where HSC cell are seen on top while HTM cells can been seen through the pores of the scaffold. We were able to establish continuous monolayers of both cell types on each side of the scaffold (Fig 1C). The cells maintained the expression of their cell type specific markers and are biologically flow responsive.

 
Conclusions
 

We have successfully engineered an in vitro biomimetic conventional outflow tract which shares many of the characteristics of the human tissue. Further development will allow this artificial outflow system to be used in studying the physiology and pathology of glaucoma and ultimately the development of improved therapeutics.

  
Keywords: 633 outflow: trabecular meshwork • 735 trabecular meshwork • 568 intraocular pressure  
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