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

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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.

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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.

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Author notes

  1. John J. E. Mulvihill and Julia Raykin contributed equally to this work.

Authors and Affiliations

  1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Dr. NW, Atlanta, GA, 30332, USA

    John J. E. Mulvihill, Julia Raykin, Eric J. Snider, Lisa A. Schildmeyer, Irsham Zaman, Manu O. Platt & C. Ross Ethier

  2. Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland

    John J. E. Mulvihill & Daniel J. Kelly

  3. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    C. Ross Ethier

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Correspondence to C. Ross Ethier.

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Associate Editor Joel D. Stitzel oversaw the review of this article.

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Mulvihill, J.J.E., Raykin, J., Snider, E.J. et al. Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels. Ann Biomed Eng 46, 365–374 (2018). https://doi.org/10.1007/s10439-017-1967-5

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