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An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures
Glaucoma is a leading cause of blindness characterized by progressive degeneration of retinal ganglion cells (RGCs). A well-established risk factor for the development and progression of glaucoma is elevation of intraocular pressure (IOP). However, how elevated IOP leads to RGC degeneration remains...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588599/ https://www.ncbi.nlm.nih.gov/pubmed/31227762 http://dx.doi.org/10.1038/s41598-019-45510-7 |
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author | Wu, Jing Mak, Heather Kayew Chan, Yau Kei Lin, Chen Kong, Cihang Leung, Christopher Kai Shun Shum, Ho Cheung |
author_facet | Wu, Jing Mak, Heather Kayew Chan, Yau Kei Lin, Chen Kong, Cihang Leung, Christopher Kai Shun Shum, Ho Cheung |
author_sort | Wu, Jing |
collection | PubMed |
description | Glaucoma is a leading cause of blindness characterized by progressive degeneration of retinal ganglion cells (RGCs). A well-established risk factor for the development and progression of glaucoma is elevation of intraocular pressure (IOP). However, how elevated IOP leads to RGC degeneration remains poorly understood. Here, we fabricate a facile, tunable hydrostatic pressure platform to study the effect of increased hydrostatic pressure on RGC axon and total neurite length, cell body area, dendritic branching, and cell survival. The hydrostatic pressure can be adjusted by varying the height of a liquid reservoir attached to a three-dimensional (3D)-printed adapter. The proposed platform enables long-term monitoring of primary RGCs in response to various pressure levels. Our results showed pressure-dependent changes in the axon length, and the total neurite length. The proportion of RGCs with neurite extensions significantly decreased by an average of 38 ± 2% (mean ± SEM) at pressures 30 mmHg and above (p < 0.05). The axon length and total neurite length decreased at a rate of 1.65 ± 0.18 μm and 4.07 ± 0.34 μm, respectively (p < 0.001), for each mmHg increase in pressure after 72 hours pressure treatment. Dendritic branching increased by 0.20 ± 0.05 intersections/day at pressures below 25 mmHg, and decreased by 0.07 ± 0.01 intersections/day at pressures above 25 mmHg (p < 0.001). There were no significant changes in cell body area under different levels of hydrostatic pressure (p ≥ 0.05). Application of this model will facilitate studies on the biophysical mechanisms that contribute to the pathophysiology of glaucoma and provide a channel for the screening of potential pharmacological agents for neuroprotection. |
format | Online Article Text |
id | pubmed-6588599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65885992019-06-28 An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures Wu, Jing Mak, Heather Kayew Chan, Yau Kei Lin, Chen Kong, Cihang Leung, Christopher Kai Shun Shum, Ho Cheung Sci Rep Article Glaucoma is a leading cause of blindness characterized by progressive degeneration of retinal ganglion cells (RGCs). A well-established risk factor for the development and progression of glaucoma is elevation of intraocular pressure (IOP). However, how elevated IOP leads to RGC degeneration remains poorly understood. Here, we fabricate a facile, tunable hydrostatic pressure platform to study the effect of increased hydrostatic pressure on RGC axon and total neurite length, cell body area, dendritic branching, and cell survival. The hydrostatic pressure can be adjusted by varying the height of a liquid reservoir attached to a three-dimensional (3D)-printed adapter. The proposed platform enables long-term monitoring of primary RGCs in response to various pressure levels. Our results showed pressure-dependent changes in the axon length, and the total neurite length. The proportion of RGCs with neurite extensions significantly decreased by an average of 38 ± 2% (mean ± SEM) at pressures 30 mmHg and above (p < 0.05). The axon length and total neurite length decreased at a rate of 1.65 ± 0.18 μm and 4.07 ± 0.34 μm, respectively (p < 0.001), for each mmHg increase in pressure after 72 hours pressure treatment. Dendritic branching increased by 0.20 ± 0.05 intersections/day at pressures below 25 mmHg, and decreased by 0.07 ± 0.01 intersections/day at pressures above 25 mmHg (p < 0.001). There were no significant changes in cell body area under different levels of hydrostatic pressure (p ≥ 0.05). Application of this model will facilitate studies on the biophysical mechanisms that contribute to the pathophysiology of glaucoma and provide a channel for the screening of potential pharmacological agents for neuroprotection. Nature Publishing Group UK 2019-06-21 /pmc/articles/PMC6588599/ /pubmed/31227762 http://dx.doi.org/10.1038/s41598-019-45510-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wu, Jing Mak, Heather Kayew Chan, Yau Kei Lin, Chen Kong, Cihang Leung, Christopher Kai Shun Shum, Ho Cheung An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
title | An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
title_full | An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
title_fullStr | An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
title_full_unstemmed | An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
title_short | An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
title_sort | in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588599/ https://www.ncbi.nlm.nih.gov/pubmed/31227762 http://dx.doi.org/10.1038/s41598-019-45510-7 |
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