TY - JOUR
T1 - Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels
T2 - Compression of Astrocytes in Collagen Gels
AU - Mulvihill, John
AU - Raykin, Julia
AU - Snider, Eric J.
AU - Schildmeyer, Lisa A.
AU - Zaman, Irsham
AU - Platt, Manu O.
AU - Kelly, Daniel J.
AU - Ethier, C. Ross
N1 - Publisher Copyright:
© 2017, Biomedical Engineering Society.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - 3D culture model
KW - Astrocyte mechanobiology
KW - Glaucoma
KW - Mechanical conditioning
KW - Optic nerve head
UR - http://www.scopus.com/inward/record.url?scp=85035085793&partnerID=8YFLogxK
U2 - 10.1007/s10439-017-1967-5
DO - 10.1007/s10439-017-1967-5
M3 - Article
C2 - 29181720
AN - SCOPUS:85035085793
SN - 0090-6964
VL - 46
SP - 365
EP - 374
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
IS - 2
ER -