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Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 01/01/2021  
Task Last Updated: 03/26/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  Ph.D. NASA Ames Research Center 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Theriot, Corey  Ph.D. University of Texas Medical Branch-Wyle 
Key Personnel Changes / Previous PI: November 2019: Corey Theriot, PhD, is now CoInvestigator per HRP; Patricia Chevez-Barrios is also CoInvestigator at this time. January 2014 report: Addition of Patricia Chevez-Barrios (collaborator, The Methodist Hospital, Houston) for ocular pathology
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 1/1/2021; note also with PI move to imec USA-Florida, PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2019 per JSC HRP; PI at Universities Space Research Association for a period; now back at NASA JSC (KBRwyle) (Ed., 11/19/18)

NOTE: This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/HRP (Ed., 8/31/16)

Task Description: An animal ground-analog is being tested as a model to induce cephalad fluid shifts and evaluate whether ocular structural changes similar to those produced in humans after exposure to a microgravity environment occur in rodents subjected to tail suspension. In vivo ocular measures and tissue analysis were performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), and optical coherence tomography (OCT) scans of the retina were evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized analysis of retinal flat mounts specifically stained to image the microvasculature. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, whole transcriptome gene expression analysis was performed and immunohistochemistry of specific markers was done on histologic sections. This study will lead to better characterization and problem definition of the Spaceflight Associated Neuro-Ocular Syndrome (SANS), and in turn, it will evaluate the need for countermeasures to mitigate the risk.

NOTE (Ed., July 2019): PI now with imec USA; PI still resides in Houston and works remotely with FL office.

NOTE (Ed., December 2018): PI at Universities Space Research Association for a period; now back at NASA JSC (KBRwyle) as internal project.

NOTE (Ed., 8/31/16): This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/Johnson Space Center Human Research Program.

Research Impact/Earth Benefits: Mechanical and oxidative stress anticipated to occur due to the fluid shift caused by hindlimb suspension are thought to be common occurrences in ophthalmic conditions on Earth, namely glaucoma, diabetic retinopathy, macular degeneration. Molecular pathways implicated in the histopathology of SANS may shed light on common mechanisms shared with the above mentioned Earth-bound diseases, and thus, in future therapies to prevent and/or ameliorate these disease conditions.

Task Progress & Bibliography Information FY2021 
Task Progress: The Spaceflight Associated Neuro-ocular Syndrome (SANS) observed in astronauts is hypothesized to be associated with microgravity-induced fluid shifts. Presently, there is a need for an animal model of SANS in order to investigate its pathophysiology. We used the rat hindlimb suspension (HS) model to examine the relationship between the assumed cephalad fluid shifts, intraocular (IOP) pressure, and the molecular responses to the prolonged change in body posture elicited in the retina in order to assess its value as a model of SANS. Young male, young female, and old male Long Evans rats were subjected to HS up to 90 days. Animals completing 90-day suspension were further studied for recovery periods up to 90 additional days at normal posture. IOP measures showed elevated pressure in HS animals for all cohorts with differences in the course of the response between the cohorts. Transcriptomics evidence supported a response to HS in the rat retina that was affected by age and sex. Several molecular networks were identified that suggest stress imposed by HS affected the retinal vasculature, oxidative and inflammation status, pigmented epithelium function, and glial activation. The CSNK1A1-TP53 pathway was implicated in the response in all cohorts. The most significant gender-specific genes were involved in cytoprotection, eye development and function, and may explain gender-dependent vulnerabilities to certain eye diseases. The results presented constitute the conclusion of this study and support the hypothesis that underlying changes in the biology of the retina subjected to simulated microgravity involve both the neural and vascular retina.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Theriot CA, Chevez-Barrios P, Loughlin T, Beheshti A, Mercaldo ND, Zanello SB. "The impact of hindlimb suspension on the rat eye: A molecular and histological analysis of the retina." Gravit Space Res. 2021 Sep 17;9(1):86-103. https://doi.org/10.2478/gsr-2021-0007 , Sep-2021
Articles in Peer-reviewed Journals Lagatuz M, Vyas RJ, Predovic M, Lim S, Jacobs N, Martinho M, Valizadegan H, Kao D, Oza N, Theriot CA, Zanello SB, Taibbi G, Vizzeri G, Dupont M, Grant MB, Lindner DJ, Reinecker HC, Pinhas A, Chui TY, Rosen RB, Moldovan N, Vickerman MB, Radhakrishnan K, Parsons-Wingerter P. "Vascular patterning as integrative readout of complex molecular and physiological signaling by VESsel GENeration Analysis." J Vasc Res. 2021 Jul;58(4):207-30. Review. https://doi.org/10.1159/000514211 ; PMID: 33839725 , Jul-2021
Articles in Peer-reviewed Journals da Silveira WA, Fazelinia H, Rosenthal SB, Laiakis EC, Kim MS, Meydan C, Kidane Y, Rathi KS, Smith SM, Stear B, Ying Y, Zhang Y, Foox J, Zanello S, Crucian B, Wang D, Nugent A, Costa HA, Zwart SR, Schrepfer S, Elworth RAL, Sapoval N, Treangen T, MacKay M, Gokhale NS, Horner SM, Singh LN, Wallace DC, Willey JS, Schisler JC, Meller R, McDonald JT, Fisch KM, Hardiman G, Taylor D, Mason CE, Costes SV, Beheshti A. "Comprehensive multi-omics analysis reveals mitochondrial stress as a central biological hub for spaceflight impact." Cell. 2020 Nov 25;183(5):1185-201.e20. https://doi.org/10.1016/j.cell.2020.11.002 ; PMID: 33242417; PMCID: PMC7870178 , Nov-2020
Articles in Peer-reviewed Journals Vyas RJ, Young M, Murray MC, Predovic M, Lim S, Jacobs NM, Mason SS, Zanello SB, Taibbi G, Vizzeri G, Parsons-Wingerter P. "Decreased vascular patterning in the retinas of astronaut crew members as new measure of ocular damage in spaceflight-associated neuro-ocular syndrome." Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):34. https://doi.org/10.1167/iovs.61.14.34 ; PMID: 33372980; PMCID: PMC7774106 , Dec-2020
Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 01/01/2021  
Task Last Updated: 12/15/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  Ph.D. NASA Ames Research Center 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Theriot, Corey  Ph.D. University of Texas Medical Branch-Wyle 
Key Personnel Changes / Previous PI: November 2019: Corey Theriot, PhD, is now CoInvestigator per HRP; Patricia Chevez-Barrios is also CoInvestigator at this time. January 2014 report: Addition of Patricia Chevez-Barrios (collaborator, The Methodist Hospital, Houston) for ocular pathology
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 1/1/2021; note also with PI move to imec USA-Florida, PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2019 per JSC HRP; PI at Universities Space Research Association for a period; now back at NASA JSC (KBRwyle) (Ed., 11/19/18)

NOTE: This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/HRP (Ed., 8/31/16)

Task Description: An animal ground-analog is being tested as a model to induce cephalad fluid shifts and evaluate whether ocular structural changes similar to those produced in humans after exposure to a microgravity environment occur in rodents subjected to tail suspension. In vivo ocular measures and tissue analysis were be performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), and optical coherence tomography (OCT) scans of the retina were evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized analysis of retinal flat mounts specifically stained to image the microvasculature. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, whole transcriptome gene expression analysis was performed and immunohistochemistry of specific markers was done on histologic sections. This study will led to better characterization and problem definition of the Spaceflight Associated Neuro-Ocular Syndrome (SANS), and in turn, it will evaluate the need for countermeasures to mitigate the risk.

NOTE (Ed., July 2019): PI now with imec USA; PI still resides in Houston and works remotely with FL office.

NOTE (Ed., December 2018): PI at Universities Space Research Association for a period; now back at NASA JSC (KBRwyle) as internal project.

NOTE (Ed., 8/31/16): This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/Johnson Space Center Human Research Program.

Research Impact/Earth Benefits: Mechanical and oxidative stress anticipated to occur due to the fluid shift caused by hindlimb suspension are thought to be common occurrences in ophthalmic conditions on Earth, namely glaucoma, diabetic retinopathy, macular degeneration. Molecular pathways implicated in the histopathology of SANS may shed light on common mechanisms shared with the above mentioned Earth-bound diseases, and thus, in future therapies to prevent and/or ameliorate these disease conditions.

Task Progress & Bibliography Information FY2020 
Task Progress: One of the responses to exposure to the microgravity environment is a pronounced cephalic fluid shift. This project tests the hypothesis that this fluid shift is a causative factor of the ocular changes seen in astronauts during and following long-duration spaceflight. We used the well-documented rat hindlimb suspension (HS) model to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. The experimental protocol used HS durations of 7, 14, 28, and 90 days. Subgroups of the 90-day rats were studied for recovery periods of 7, 14, 28, or 90 days. All HS animals had age-matched cage controls. All animals had ad libitum access to food and water and were maintained to a light/darkness 12:12 LD cycle. The following clinical ophthalmic measures were performed at baseline and at the conclusion of HS: IOP (by rebound tonometry), direct and indirect ophthalmoscopy, optical coherence tomography (OCT) and fundus imaging. ICP was recorded by telemetry. Eyes were collected at baseline, 7, 14, 28, and 90 days of HS, and at 7, 14, 28, and 90 days of recovery, for histologic and gene expression evaluations. This work focuses on the gene expression and histologic changes observed in the rat retina in response to HS and their relationship with ICP and IOP. Due to the multiplicity of applications for these rats, the experimental scheme was remarkably complex.

This progress report discusses the findings pertaining to the live measures obtained from the animals, namely intraocular pressure (IOP) and intracranial pressure (ICP). Optical Computerized Tomography (OCT) images were received from the collaboration team but as discussed in the previous report, the quality of the images did not allow a proper analysis.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2020
Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 01/01/2021  
Task Last Updated: 12/27/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  Ph.D. NASA Ames Research Center 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Theriot, Corey  Ph.D. University of Texas Medical Branch-Wyle 
Key Personnel Changes / Previous PI: November 2019: Corey Theriot, PhD, is now CoInvestigator per HRP; Patricia Chevez-Barrios is also CoInvestigator at this time. January 2014 report: Addition of Patricia Chevez-Barrios (collaborator, The Methodist Hospital, Houston) for ocular pathology
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 1/1/2021; note also with PI move to imec USA-Florida, PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2019 per JSC HRP; PI at Universities Space Research Association for a period; now back at NASA JSC (KBRwyle) (Ed., 11/19/18)

NOTE: This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/HRP (Ed., 8/31/16)

Task Description: An animal ground-analog is being tested as a model to induce cephalad fluid shifts and evaluate whether ocular structural changes similar to those produced in humans after exposure to a microgravity environment occur in rodents subjected to tail suspension. In vivo ocular measures and tissue analysis were be performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), and optical coherence tomography (OCT) scans of the retina were evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized analysis of retinal flat mounts specifically stained to image the microvasculature. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, whole transcriptome gene expression analysis was performed and immunohistochemistry of specific markers was done on histologic sections. This study will led to better characterization and problem definition of the Spaceflight Associated Neuro-Ocular Syndrome (SANS), and in turn, it will evaluate the need for countermeasures to mitigate the risk.

NOTE (Ed., July 2019): PI now with imec USA; PI still resides in Houston and works remotely with FL office.

NOTE (Ed., Dec 2018): PI at Universities Space Research Association for a period; now back at NASA JSC (KBRwyle) as internal project.

NOTE (Ed., 8/31/16): This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/Johnson Space Center Human Research Program.

Research Impact/Earth Benefits: Mechanical and oxidative stress anticipated to occur due to the fluid shift caused by hindlimb suspension are thought to be common occurrences in ophthalmic conditions on Earth, namely glaucoma, diabetic retinopathy, macular degeneration. Molecular pathways implicated in the histopathology of SANS may shed light on common mechanisms shared with the above mentioned Earth-bound diseases, and thus, in future therapies to prevent and/or ameliorate these diseases conditions.

Task Progress & Bibliography Information FY2019 
Task Progress: One of the responses to exposure to the microgravity environment is a pronounced cephalic fluid shift. This project tests the hypothesis that this fluid shift is a causative factor of the ocular changes seen in astronauts during and following long-duration spaceflight. We are using the well-documented rat hindlimb suspension (HS) model to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. The experimental protocol uses HS durations of 7, 14, 28, and 90 days. Subgroups of the 90-day rats are studied for recovery periods of 7, 14, 28, or 90 days. All HS animals have age-matched cage controls. All animals have ad libitum access to food and water. A 12:12 LD (light dark) cycle is present. The following clinical ophthalmic measures are performed on all subjects at baseline and at the conclusion of HS: IOP (by rebound tonometry), direct and indirect ophthalmoscopy, optical coherence tomography (OCT), and fundus imaging. Eyes are collected at baseline, 7, 14, 28, and 90 days of HS, and at 7, 14, 28, and 90 days of recovery, for histologic and gene expression evaluations. This work centers on the gene expression and histologic changes observed in the rat retina in response to HS and their relationship with ICP and IOP.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2019
Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 09/30/2019  
Task Last Updated: 11/06/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  Ph.D. NASA Glenn Research Center 
Vizzeri, Gianmarco  M.D. University of Texas Medical Branch 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Key Personnel Changes / Previous PI: January 2014 report: Addition of Patricia Chevez-Barrios (collaborator, The Methodist Hospital, Houston) for ocular pathology
Project Information: Grant/Contract No. NNX15AW48G ; Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NNX15AW48G ; Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 9/30/2019 per HRP (Ed., 11/19/18)

NOTE: This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/HRP (Ed., 8/31/16)

Task Description: An animal ground-analog is proposed for validation as a model to induce cephalad fluid shifts and evaluate ocular structural changes similar to those produced in humans after exposure to a microgravity environment. In vivo ocular measures and tissue analysis will be performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), fluorescein angiography (FA), optical coherence tomography (OCT) scans of the retina, and ultrasound of the optic nerve will be evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized quantitative analysis of FA and retinal flat mounts. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, markers of oxidative stress, hypoxia, and cellular death will be investigated by gene expression analysis and immunohistochemistry. This study will lead to better characterization and problem definition of the Visual Impairment and Intracranial Pressure (VIIP) risk, and in turn, it will evaluate the need for countermeasures to mitigate this risk.

NOTE (Ed., 8/31/16): This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/Johnson Space Center Human Research Program

Research Impact/Earth Benefits: Mechanical and oxidative stress anticipated to occur due to the fluid shift caused by hindlimb suspension are thought to be common occurrences in ophthalmic conditions on Earth, namely glaucoma, diabetic retinopathy, macular degeneration. Molecular pathways implicated in the histopahtology of VIIP may shed light on common mechanisms shared with the above mentioned Earth-bound diseases, and thus, in future therapies to prevent and/or ameliorate these diseases conditions.

Task Progress & Bibliography Information FY2017 
Task Progress: The progress in this study has been consistent and centered on running the animal study. This stage is very involved, as it requires many animals, some of which are maintained in the study for a long period of time (up to 180 days). These activities are being performed at another facility (University of California Davis, Laboratory of Dr. Charles Fuller). There have been some delays in this process that have affected our ability to proceed with the analysis of samples. However, samples are being frequently received at our laboratory and analysis will begin during the course of FY17.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2017
Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 09/30/2018  
Task Last Updated: 11/28/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  NASA Glenn Research Center 
Vizzeri, Gianmarco  University of Texas Medical Branch 
Chevez-Barrios, Patricia  The Methodist Hospital Research Institute 
Key Personnel Changes / Previous PI: January 2014 report: Addition of Patricia Chevez-Barrios (collaborator, The Methodist Hospital, Houston) for ocular pathology
Project Information: Grant/Contract No. NNX15AW48G ; Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NNX15AW48G ; Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/HRP (Ed., 8/31/16)

Task Description: An animal ground-analog is proposed for validation as a model to induce cephalad fluid shifts and evaluate ocular structural changes similar to those produced in humans after exposure to a microgravity environment. In vivo ocular measures and tissue analysis will be performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), fluorescein angiography (FA), optical coherence tomography (OCT) scans of the retina, and ultrasound of the optic nerve will be evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized quantitative analysis of FA and retinal flat mounts. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, markers of oxidative stress, hypoxia, and cellular death will be investigated by gene expression analysis and immunohistochemistry. This study will lead to better characterization and problem definition of the Visual Impairment and Intracranial Pressure risk, and in turn, it will evaluate the need for countermeasures to mitigate this risk.

NOTE (Ed., 8/31/16): This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/Johnson Space Center Human Research Program

Research Impact/Earth Benefits: Mechanical and oxidative stress anticipated to occur due to the fluid shift caused by hindlimb suspension are thought to be common occurrences in ophthalmic conditions on Earth, namely glaucoma, diabetic retinopathy, macular degeneration. Molecular pathways implicated in the histopahtology of VIIP may shed light on common mechanisms shared with the above mentioned Earth-bound diseases, and thus, in future therapies to prevent and/or ameliorate these diseases conditions.

Task Progress & Bibliography Information FY2015 
Task Progress: One of the responses to exposure to the microgravity spaceflight environment is a pronounced cephalic fluid shift. This project tests the hypothesis that this fluid shift is a causative factor in the ocular changes seen in astronauts during and following long-duration spaceflight. The study uses the well-documented rat hindlimb suspension (HLS) model to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. The experimental protocol uses HLS durations of 7, 14, 28, and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28, or 90 days. All HLS animals have age-matched cage controls. All animals have ad lib access to food and water. A 12:12 LD cycle is present. Eyes are collected at baseline, 7, 14, 28, and 90 days of HLS, and at 7, 14, 28, and 90 days of recovery, for histologic and gene expression evaluations. The study has started with the young adult male and young adult female cohorts. Comparing data between these cohorts will allow to determine if there is a gender difference in the responses. Following completion of these two groups, there will be two additional cohorts: older middle-age adult males and a group exposed to elevated CO2 levels similar to those experienced on ISS. This last group will allow to determine if a mild (~1%) hypercapnic environment plays a role in the cephalic shift response and possible development of VIIP (Vision Impairment and Intracranial Pressure).

NOTE (Ed., 8/31/16): This project had some delays and is still underway with an end date now of 9/30/2018. It moved from an Internal Project to Grant NNX15AW48G starting 10/1/2015, per A. Allcorn/Johnson Space Center Human Research Program.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Glass A, Theriot C, Lam C-W, James J, Zanello S. "Wound healing response to lunar dust exposure in the rat cornea." Presented at 65th International Astronautics Congress (IAC 2014), Toronto, Canada, September 29-October 2, 2014.

65th International Astronautics Congress (IAC 2014), Toronto, Canada, September 29-October 2, 2014. , Sep-2014

Articles in Peer-reviewed Journals Theriot C, Zanello S. "Molecular effects of spaceflight in the mouse eye after Shuttle Mission STS-135." Gravitational and Space Research. 2014 Aug;2(1):3-14. http://gravitationalandspacebiology.org/index.php/journal/article/view/643 ; accessed 12/3/14. , Aug-2014
Articles in Peer-reviewed Journals Taibbi G, Cromwell RL, Zanello SB, Yarbough PO, Ploutz-Snyder RJ, Godley BF, Vizzeri G. "Ocular outcomes evaluation in a 14-day head-down bed rest study." Aviation, Space, and Environmental Medicine. 2014 Oct;85(10):983-92. PubMed PMID: 25245897; PubMed Central PMCID: PMC4240225 , Oct-2014
Journal/Magazine covers Theriot C, Zanello S. "Cover in journal Gravitational and Space Research for article, 'Molecular effects of spaceflight in the mouse eye after Shuttle Mission STS-135.' " Gravitational and Space Research. 2014 Aug;2(1):3-14. http://gravitationalandspaceresearch.org/index.php/journal/issue/view/51 ; accessed 4/1/21. , Aug-2014
Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 09/30/2015  
Task Last Updated: 01/07/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  NASA Glenn Research Center 
Vizzeri, Gianmarco  University of Texas Medical Branch 
Key Personnel Changes / Previous PI: January 2014 report: Addition of Patricia Chevez-Barrios (collaborator, The Methodist Hospital, Houston) for ocular pathology
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Task Description: An animal ground-analog is proposed for validation as a model to induce cephalad fluid shifts and evaluate ocular structural changes similar to those produced in humans after exposure to a microgravity environment. In vivo ocular measures and tissue analysis will be performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), fluorescein angiography (FA), optical coherence tomography (OCT) scans of the retina, and ultrasound of the optic nerve will be evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized quantitative analysis of FA and retinal flat mounts. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, markers of oxidative stress, hypoxia, and cellular death will be investigated by gene expression analysis and immunohistochemistry. This study will lead to better characterization and problem definition of the Visual Impairment and Intracranial Pressure risk, and in turn, it will evaluate the need for countermeasures to mitigate this risk.

Research Impact/Earth Benefits: Mechanical and oxidative stress anticipated to occur due to the fluid shift caused by hindlimb suspension are thought to be common occurrences in ophthalmic conditions on Earth, namely glaucoma, diabetic retinopathy, macular degeneration. Molecular pathways implicated in the histopahtology of VIIP may shed light on common mechanisms shared with the above mentioned Earth-bound diseases, and thus, in future therapies to prevent and/or ameliorate these diseases conditions.

Task Progress & Bibliography Information FY2014 
Task Progress: Our project investigates whether rodent hindlimb suspension (HS) is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature, and acquisition of high quality images suitable for VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. In summary, we have an improved method for studying the retinal microvasculature that will provide an increase in the quality of images captured and will be applied throughout the various animal cohorts of the recently-initiated study that will evaluate rodent HS as a model to study ophthalmic complications in microgravity.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Zanello SB, Theriot CA, Prospero Ponce CM, Chevez-Barrios P. "Spaceflight effects and molecular responses in the mouse eye: Observations after Shuttle Mission STS-133." Gravit Space Res. 2013 Oct;1(1):29-46. http://gravitationalandspacebiology.org/index.php/journal/issue/view/49/showToc , Oct-2013
Articles in Peer-reviewed Journals Zanello S, Nguyen A,Theriot C. "Retinal non-visual photoreception in space." Aviat Space Environ Med. 2013 Dec;84(12):1277-80. http://dx.doi.org/10.3357/ASEM.3762.2013 , Dec-2013
Articles in Peer-reviewed Journals Taibbi G, Kaplowitz K, Cromwell RL, Godley BF, Zanello SB, Vizzeri G. "Effects of 30-day head-down bed rest on ocular structures and visual function in a healthy subject." Aviat Space Environ Med. 2013 Feb;84(2):148-54. PMID: 23447853 , Feb-2013
Awards VIIP Group. "NASA Honor Group Achievement Award, August 2013." Aug-2013
NASA Technical Documents Alexander D GR, Hamilton D, Lee S, Mader T, Otto C, Oubre C, Pass A, Platts S, Scott J, Smith S, Stenger M, Westby C, Zanello S. "Evidence Report: Risk of Spaceflight-Induced Intracranial Hypertension and Vision Alterations." Evidence Book for HRP Roadmap, 2012. http://humanresearchroadmap.nasa.gov/Evidence/ ; accessed 1/7/14. , Jul-2012
Project Title:  Evaluation of Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity: Ocular Structure and Function and Association with Intracranial Pressure Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 02/01/2013  
End Date: 09/30/2015  
Task Last Updated: 04/12/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Parsons-Wingerter, Patricia  NASA Glenn Research Center 
Vizzeri, Gianmarco  University of Texas Medical Branch 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Villarreal, Jennifer  
Center Contact: 281-483-7306 
jennifer.v311larreal@nasa.gov 
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Task Description: An animal ground-analog is proposed for validation as a model to induce cephalad fluid shifts and evaluate ocular structural changes similar to those produced in humans after exposure to a microgravity environment. In vivo ocular measures and tissue analysis will be performed in hindlimb suspension (HS) and normal posture control rats. Intraocular pressure (IOP), intracranial pressure (ICP), fluorescein angiography (FA), optical coherence tomography (OCT) scans of the retina and ultrasound of the optic nerve will be evaluated before, during, and after HS. Retinal microvascular changes will be evaluated by computerized quantitative analysis of FA and retinal flat mounts. In order to study cellular responses that are possibly associated with the stress of variations in translaminar pressure in the retina due to cephalad fluid shift, markers of oxidative stress, hypoxia, and cellular death will be investigated by gene expression analysis and immunohistochemistry. This study will lead to better characterization and problem definition of the Visual Impairment and Intracranial Pressure (VIIP) risk, and in turn, it will evaluate the need for countermeasures to mitigate this risk.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2013 
Task Progress: New project for FY2013.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2013