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

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 transform...

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Bibliographic Details
Published in:	Annals of biomedical engineering Vol. 46; no. 2; pp. 365 - 374
Main Authors:	Mulvihill, John J. E., Raykin, Julia, Snider, Eric J., Schildmeyer, Lisa A., Zaman, Irsham, Platt, Manu O., Kelly, Daniel J., Ethier, C. Ross
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-02-2018 Springer Nature B.V
Subjects:	Animals Astrocytes Astrocytes - metabolism Astrocytes - pathology Biochemistry Biological and Medical Physics Biomechanics Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Biophysics Cell culture Cell Culture Techniques Cell death Cell Hypoxia Cell Line Classical Mechanics Collagen Collagen - chemistry Compression Compressive Strength Deformation mechanisms Gels Genetic transformation Glaucoma Glaucoma - metabolism Glaucoma - pathology Glaucoma - physiopathology Glial fibrillary acidic protein Hypoxia Intraocular Pressure Mechanical stimuli Models, Biological Optic nerve Optic neuropathy Pathogenesis Rats Retina Risk factors Vimentin Glaucoma Optic nerve head 3D culture model Astrocyte mechanobiology Mechanical conditioning
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0090-6964 1573-9686
DOI:	10.1007/s10439-017-1967-5