Simulation of murine retinal hemodynamics in response to tail suspension
The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction. Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained a...
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creator | Caddy, Harrison T. Fujino, Mitsunori Vahabli, Ebrahim Voigt, Valentina Kelsey, Lachlan J. Dilley, Rodney J. Carvalho, Livia S. Takahashi, Satoru Green, Daniel J. Doyle, Barry J. |
description | The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction.
Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution.
TS samples exhibited reduced surface area (4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2, P = 0.010) and shorter lengths between branches in small vessels ( |
doi_str_mv | 10.1016/j.compbiomed.2024.109148 |
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Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution.
TS samples exhibited reduced surface area (4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2, P = 0.010) and shorter lengths between branches in small vessels (<10 μm, 69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm, P < 0.001). Wall shear stress (WSS) and pressure were higher in TS mice compared to controls, particularly in smaller vessels (<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004). Rates of retinal endothelial cell death were variable in TS mice compared to controls. WSS and pressure were generally higher in cell death regions, both within and between cohorts, but significance was variable and limited to small to medium-sized vessels (<20 μm).
These findings suggest a link may exist between emulated microgravity and retinal endothelial dysfunction that may have implications for SANS development. Future work with increased sample sizes of larger species or spaceflight cohorts should be considered.
[Display omitted]
•Investigated retinal endothelial dysfunction in control and tail suspended mice.•Custom workflow combined confocal imaging, 3D model generation and fluid simulation.•Retinal endothelial cell death varied in tail suspended mice compared to controls.•Shear stress and pressure higher in small retinal vessels of tail suspended mice.•Emulated microgravity hemodynamics may be linked to endothelial dysfunction.</description><identifier>ISSN: 0010-4825</identifier><identifier>ISSN: 1879-0534</identifier><identifier>EISSN: 1879-0534</identifier><identifier>DOI: 10.1016/j.compbiomed.2024.109148</identifier><identifier>PMID: 39298883</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Aerospace environments ; Animals ; Blood flow ; Blood pressure ; Boundary conditions ; Capillary flow ; Capillary pressure ; Cell death ; Computational fluid dynamics ; Computer Simulation ; Edema ; Endothelial cells ; Experiments ; Flow distribution ; Fluid flow ; Fluid pressure ; Hemodynamics ; Hemodynamics - physiology ; Hindlimb Suspension - physiology ; Male ; Mice ; Mice, Inbred C57BL ; Microgravity ; Mouse ; Pressure effects ; Radiation ; Retina ; Retina - physiology ; Retinal Vessels - physiology ; Rodents ; SANS ; Simulation ; Space flight ; Tail suspension ; Veins & arteries ; Vessels ; Wall shear stresses ; Weightlessness ; Workflow</subject><ispartof>Computers in biology and medicine, 2024-11, Vol.182, p.109148, Article 109148</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2024. The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1923-42ec81f5120dc6bf9ed2df90cb57a066b59c790a895493531e48b25407d110233</cites><orcidid>0000-0003-4923-2796 ; 0000-0003-3226-2921 ; 0000-0002-3151-507X ; 0000-0003-0147-8113</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0010482524012332$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39298883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caddy, Harrison T.</creatorcontrib><creatorcontrib>Fujino, Mitsunori</creatorcontrib><creatorcontrib>Vahabli, Ebrahim</creatorcontrib><creatorcontrib>Voigt, Valentina</creatorcontrib><creatorcontrib>Kelsey, Lachlan J.</creatorcontrib><creatorcontrib>Dilley, Rodney J.</creatorcontrib><creatorcontrib>Carvalho, Livia S.</creatorcontrib><creatorcontrib>Takahashi, Satoru</creatorcontrib><creatorcontrib>Green, Daniel J.</creatorcontrib><creatorcontrib>Doyle, Barry J.</creatorcontrib><title>Simulation of murine retinal hemodynamics in response to tail suspension</title><title>Computers in biology and medicine</title><addtitle>Comput Biol Med</addtitle><description>The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction.
Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution.
TS samples exhibited reduced surface area (4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2, P = 0.010) and shorter lengths between branches in small vessels (<10 μm, 69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm, P < 0.001). Wall shear stress (WSS) and pressure were higher in TS mice compared to controls, particularly in smaller vessels (<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004). Rates of retinal endothelial cell death were variable in TS mice compared to controls. WSS and pressure were generally higher in cell death regions, both within and between cohorts, but significance was variable and limited to small to medium-sized vessels (<20 μm).
These findings suggest a link may exist between emulated microgravity and retinal endothelial dysfunction that may have implications for SANS development. Future work with increased sample sizes of larger species or spaceflight cohorts should be considered.
[Display omitted]
•Investigated retinal endothelial dysfunction in control and tail suspended mice.•Custom workflow combined confocal imaging, 3D model generation and fluid simulation.•Retinal endothelial cell death varied in tail suspended mice compared to controls.•Shear stress and pressure higher in small retinal vessels of tail suspended mice.•Emulated microgravity hemodynamics may be linked to endothelial dysfunction.</description><subject>Aerospace environments</subject><subject>Animals</subject><subject>Blood flow</subject><subject>Blood pressure</subject><subject>Boundary conditions</subject><subject>Capillary flow</subject><subject>Capillary pressure</subject><subject>Cell death</subject><subject>Computational fluid dynamics</subject><subject>Computer Simulation</subject><subject>Edema</subject><subject>Endothelial cells</subject><subject>Experiments</subject><subject>Flow distribution</subject><subject>Fluid flow</subject><subject>Fluid pressure</subject><subject>Hemodynamics</subject><subject>Hemodynamics - physiology</subject><subject>Hindlimb Suspension - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microgravity</subject><subject>Mouse</subject><subject>Pressure effects</subject><subject>Radiation</subject><subject>Retina</subject><subject>Retina - physiology</subject><subject>Retinal Vessels - physiology</subject><subject>Rodents</subject><subject>SANS</subject><subject>Simulation</subject><subject>Space flight</subject><subject>Tail suspension</subject><subject>Veins & arteries</subject><subject>Vessels</subject><subject>Wall shear stresses</subject><subject>Weightlessness</subject><subject>Workflow</subject><issn>0010-4825</issn><issn>1879-0534</issn><issn>1879-0534</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQhkVpabZp_0IR5JKLt6MvWzomIWkKgR7anoUsj6kWW3IkO5B_Xy2bUOilp4GZ551hHkIogz0D1n457H2alz6kGYc9By5r2zCp35Ad051pQAn5luwAGDRSc3VGPpRyAAAJAt6TM2G40VqLHbn_EeZtcmtIkaaRzlsOEWnGNUQ30d84p-E5ujn4QkOs_bKkWJCuia4uTLRsZcFYavojeTe6qeCnl3pOft3d_ry5bx6-f_12c_XQeGa4aCRHr9moGIfBt_1ocODDaMD3qnPQtr0yvjPgtFHSCCUYSt1zJaEbGAMuxDm5PO1dcnrcsKx2DsXjNLmIaStWMOiY6qqMil78gx7SlutfR4orY1rRtZXSJ8rnVErG0S45zC4_Wwb2aNse7F_b9mjbnmzX6OeXA1t_nL0GX_VW4PoEYDXyFDDb4gNGj0PI6Fc7pPD_K38AxUeUZg</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Caddy, Harrison T.</creator><creator>Fujino, Mitsunori</creator><creator>Vahabli, Ebrahim</creator><creator>Voigt, Valentina</creator><creator>Kelsey, Lachlan J.</creator><creator>Dilley, Rodney J.</creator><creator>Carvalho, Livia S.</creator><creator>Takahashi, Satoru</creator><creator>Green, Daniel J.</creator><creator>Doyle, Barry J.</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>JQ2</scope><scope>K9.</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4923-2796</orcidid><orcidid>https://orcid.org/0000-0003-3226-2921</orcidid><orcidid>https://orcid.org/0000-0002-3151-507X</orcidid><orcidid>https://orcid.org/0000-0003-0147-8113</orcidid></search><sort><creationdate>202411</creationdate><title>Simulation of murine retinal hemodynamics in response to tail suspension</title><author>Caddy, Harrison T. ; Fujino, Mitsunori ; Vahabli, Ebrahim ; Voigt, Valentina ; Kelsey, Lachlan J. ; Dilley, Rodney J. ; Carvalho, Livia S. ; Takahashi, Satoru ; Green, Daniel J. ; Doyle, Barry J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1923-42ec81f5120dc6bf9ed2df90cb57a066b59c790a895493531e48b25407d110233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aerospace environments</topic><topic>Animals</topic><topic>Blood flow</topic><topic>Blood pressure</topic><topic>Boundary conditions</topic><topic>Capillary flow</topic><topic>Capillary pressure</topic><topic>Cell death</topic><topic>Computational fluid dynamics</topic><topic>Computer Simulation</topic><topic>Edema</topic><topic>Endothelial cells</topic><topic>Experiments</topic><topic>Flow distribution</topic><topic>Fluid flow</topic><topic>Fluid pressure</topic><topic>Hemodynamics</topic><topic>Hemodynamics - physiology</topic><topic>Hindlimb Suspension - physiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microgravity</topic><topic>Mouse</topic><topic>Pressure effects</topic><topic>Radiation</topic><topic>Retina</topic><topic>Retina - physiology</topic><topic>Retinal Vessels - physiology</topic><topic>Rodents</topic><topic>SANS</topic><topic>Simulation</topic><topic>Space flight</topic><topic>Tail suspension</topic><topic>Veins & arteries</topic><topic>Vessels</topic><topic>Wall shear stresses</topic><topic>Weightlessness</topic><topic>Workflow</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caddy, Harrison T.</creatorcontrib><creatorcontrib>Fujino, Mitsunori</creatorcontrib><creatorcontrib>Vahabli, Ebrahim</creatorcontrib><creatorcontrib>Voigt, Valentina</creatorcontrib><creatorcontrib>Kelsey, Lachlan J.</creatorcontrib><creatorcontrib>Dilley, Rodney J.</creatorcontrib><creatorcontrib>Carvalho, Livia S.</creatorcontrib><creatorcontrib>Takahashi, Satoru</creatorcontrib><creatorcontrib>Green, Daniel J.</creatorcontrib><creatorcontrib>Doyle, Barry J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Computers in biology and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caddy, Harrison T.</au><au>Fujino, Mitsunori</au><au>Vahabli, Ebrahim</au><au>Voigt, Valentina</au><au>Kelsey, Lachlan J.</au><au>Dilley, Rodney J.</au><au>Carvalho, Livia S.</au><au>Takahashi, Satoru</au><au>Green, Daniel J.</au><au>Doyle, Barry J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simulation of murine retinal hemodynamics in response to tail suspension</atitle><jtitle>Computers in biology and medicine</jtitle><addtitle>Comput Biol Med</addtitle><date>2024-11</date><risdate>2024</risdate><volume>182</volume><spage>109148</spage><pages>109148-</pages><artnum>109148</artnum><issn>0010-4825</issn><issn>1879-0534</issn><eissn>1879-0534</eissn><abstract>The etiology of spaceflight-associated neuro-ocular syndrome (SANS) remains unclear. Recent murine studies indicate there may be a link between the space environment and retinal endothelial dysfunction.
Post-fixed control (N = 4) and 14-day tail-suspended (TS) (N = 4) mice eye samples were stained and imaged for the vessel plexus and co-located regions of endothelial cell death. A custom workflow combined whole-mounted and tear reconstructed three-dimensional (3D) spherical retinal plexus models with computational fluid dynamics (CFD) simulation that accounted for the Fåhræus-Lindqvist effect and boundary conditions that accommodated TS fluid pressure measurements and deeper capillary layer blood flow distribution.
TS samples exhibited reduced surface area (4.6 ± 0.5 mm2 vs. 3.5 ± 0.3 mm2, P = 0.010) and shorter lengths between branches in small vessels (<10 μm, 69.5 ± 0.6 μm vs. 60.4 ± 1.1 μm, P < 0.001). Wall shear stress (WSS) and pressure were higher in TS mice compared to controls, particularly in smaller vessels (<10 μm, WSS: 6.57 ± 1.08 Pa vs. 4.72 ± 0.67 Pa, P = 0.034, Pressure: 72.04 ± 3.14 mmHg vs. 50.64 ± 6.74 mmHg, P = 0.004). Rates of retinal endothelial cell death were variable in TS mice compared to controls. WSS and pressure were generally higher in cell death regions, both within and between cohorts, but significance was variable and limited to small to medium-sized vessels (<20 μm).
These findings suggest a link may exist between emulated microgravity and retinal endothelial dysfunction that may have implications for SANS development. Future work with increased sample sizes of larger species or spaceflight cohorts should be considered.
[Display omitted]
•Investigated retinal endothelial dysfunction in control and tail suspended mice.•Custom workflow combined confocal imaging, 3D model generation and fluid simulation.•Retinal endothelial cell death varied in tail suspended mice compared to controls.•Shear stress and pressure higher in small retinal vessels of tail suspended mice.•Emulated microgravity hemodynamics may be linked to endothelial dysfunction.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>39298883</pmid><doi>10.1016/j.compbiomed.2024.109148</doi><orcidid>https://orcid.org/0000-0003-4923-2796</orcidid><orcidid>https://orcid.org/0000-0003-3226-2921</orcidid><orcidid>https://orcid.org/0000-0002-3151-507X</orcidid><orcidid>https://orcid.org/0000-0003-0147-8113</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aerospace environments Animals Blood flow Blood pressure Boundary conditions Capillary flow Capillary pressure Cell death Computational fluid dynamics Computer Simulation Edema Endothelial cells Experiments Flow distribution Fluid flow Fluid pressure Hemodynamics Hemodynamics - physiology Hindlimb Suspension - physiology Male Mice Mice, Inbred C57BL Microgravity Mouse Pressure effects Radiation Retina Retina - physiology Retinal Vessels - physiology Rodents SANS Simulation Space flight Tail suspension Veins & arteries Vessels Wall shear stresses Weightlessness Workflow |
title | Simulation of murine retinal hemodynamics in response to tail suspension |
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