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Annals of Biomedical Engineering

, Volume 46, Issue 2, pp 365–374 | Cite as

Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels

  • John J. E. Mulvihill
  • Julia Raykin
  • Eric J. Snider
  • Lisa A. Schildmeyer
  • Irsham Zaman
  • Manu O. Platt
  • Daniel J. Kelly
  • C. Ross Ethier
Article

Abstract

Glaucoma is a common optic neuropathy characterized by retinal ganglion cell death. Elevated intraocular pressure (IOP), a key risk factor for glaucoma, leads to significant biomechanical deformation of optic nerve head (ONH) cells and tissues. ONH astrocytes respond to this deformation by transforming to a reactive, proliferative phenotype, which has been implicated in the progression of glaucomatous vision loss. However, little is known about the mechanisms of this transformation. In this study, we developed a 3D collagen gel culture system to mimic features of ONH deformation due to elevated IOP. Compressive loading of astrocyte-seeded collagen gels led to cell alignment perpendicular to the direction of strain, and increased astrocyte activation, as assayed by GFAP, vimentin, and s100β levels, as well as MMP activity. This proof-of-concept study shows that this system has potential for studying mechanisms of astrocyte mechanobiology as related to the pathogenesis of glaucoma. Further work is needed to establish the possible interplay of mechanical stimulation, matrix properties, and hypoxia on the observed response of astrocytes.

Keywords

Glaucoma Astrocyte mechanobiology Optic nerve head 3D culture model Mechanical conditioning 

Notes

Acknowledgments

This work was supported by the Georgia Research Alliance, the Irish Research Council through the ELEVATE: Irish Research Council International Career Development Fellowship—co-funded by Marie Curie Actions, the National Space Biomedical Research Institute through NCC 9-58, and the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1148903.

Supplementary material

10439_2017_1967_MOESM1_ESM.pdf (1.9 mb)
Supplementary material 1 (PDF 1976 kb)

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Copyright information

© Biomedical Engineering Society 2017

Authors and Affiliations

  1. 1.Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityAtlantaUSA
  2. 2.Department of Mechanical and Manufacturing Engineering, School of EngineeringTrinity College DublinDublinIreland
  3. 3.George W. Woodruff School of Mechanical Engineering, Georgia Institute of TechnologyAtlantaUSA

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