June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Altered Elasticity of Normal and Glaucoma Lamina Cribrosa (NLC and GLC) Cells in Response to Biophysical Stimuli
Author Affiliations & Notes
  • Baiyun Liu
    school of physics, University College dublin, Conway institute,, Dublin, Ireland
  • Jason Kilpatrick
    school of physics, University College dublin, Conway institute,, Dublin, Ireland
  • Deborah Wallace
    School of Medicine and Medical Sciences, UCD Clinical Research Centre, Dublin, Ireland
    Dept. of Ophthalmology,, Mater Misericordiae University Hospital, Dublin, Ireland
  • Colm J O'Brien
    School of Medicine and Medical Sciences, UCD Clinical Research Centre, Dublin, Ireland
    Dept. of Ophthalmology,, Mater Misericordiae University Hospital, Dublin, Ireland
  • Suzi Jarvis
    school of physics, University College dublin, Conway institute,, Dublin, Ireland
  • Footnotes
    Commercial Relationships Baiyun Liu, None; Jason Kilpatrick, None; Deborah Wallace, None; Colm O'Brien, None; Suzi Jarvis, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4824. doi:
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      Baiyun Liu, Jason Kilpatrick, Deborah Wallace, Colm J O'Brien, Suzi Jarvis; Altered Elasticity of Normal and Glaucoma Lamina Cribrosa (NLC and GLC) Cells in Response to Biophysical Stimuli. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4824.

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

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Abstract

Purpose: Abnormalities of lamina cribrosa (LC) structure have been identified in primary open angle glaucoma (POAG) patients which result in modification of tissue stiffness as a function of disease progression. By studying LC cells cultured on substrates which mimic these changes in the in vivo environment we can gain an understanding of these effects on cellular response and therefore mechanical properties of individual cells. This study allows us to directly study the influence of the cellular environment associated with disease progression on the properties of LC cells.

Methods: Primary normal and glaucoma LC cells cultured on substrates of varied stiffness served as analogs to the extracellular environments for both healthy and glaucoma patients. Cell morphology and quantification of pro-fibrotic transformation protein, alpha-smooth muscle actin (α-SMA) were studies using immunocytochemical staining and confocal microscopy. Atomic force microscopy (AFM) was used to quantify the mechanical properties of LC cells.

Results: With increasing substrate stiffness LC cells exhibited more prominent actin filaments and vinculin-containing focal adhesions, suggestive of increased cytoskeleton contractility. Increased expression of α-SMA on stiffer substrates confirmed transformation to the fibrotic phenotype. Nanoindentation testing with AFM suggests that normal and glaucoma LC cells exhibited two different mechanical response when culturing on compliant substrates with a low and high modulus. For substrates with increased stiffness, both normal and glaucoma LC cells exhibited a predominately high modulus response, with narrower distribution for glaucoma LC cells.

Conclusions: Substrate stiffness serves as a biomimetic biophysical cues which significantly modulates LC cell behavior. By studying the response of LC cells in different mechanical environments we were able to directly observe the influence of the cellular environment associated with disease progression.

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