An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures

Abstract 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...

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Autores principales:	Jing Wu, Heather Kayew Mak, Yau Kei Chan, Chen Lin, Cihang Kong, Christopher Kai Shun Leung, Ho Cheung Shum
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f0568a649344552903dab995dc4dfa5
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spelling	oai:doaj.org-article:6f0568a649344552903dab995dc4dfa52021-12-02T15:09:17ZAn in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures10.1038/s41598-019-45510-72045-2322https://doaj.org/article/6f0568a649344552903dab995dc4dfa52019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45510-7https://doaj.org/toc/2045-2322Abstract 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.Jing WuHeather Kayew MakYau Kei ChanChen LinCihang KongChristopher Kai Shun LeungHo Cheung ShumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Wu Heather Kayew Mak Yau Kei Chan Chen Lin Cihang Kong Christopher Kai Shun Leung Ho Cheung Shum An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures
description	Abstract 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	article
author	Jing Wu Heather Kayew Mak Yau Kei Chan Chen Lin Cihang Kong Christopher Kai Shun Leung Ho Cheung Shum
author_facet	Jing Wu Heather Kayew Mak Yau Kei Chan Chen Lin Cihang Kong Christopher Kai Shun Leung Ho Cheung Shum
author_sort	Jing Wu
title	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_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_sort	in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/6f0568a649344552903dab995dc4dfa5
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An in vitro pressure model towards studying the response of primary retinal ganglion cells to elevated hydrostatic pressures

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