Task Effects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits
Last Published:  07/31/19 10:05:33 AM (Central)
Short Title: Tissue Sharing Flagship
Responsible HRP Element: Human Health Countermeasures
Collaborating Org(s):
Other:
Space Radiation (SR) Element
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
Aims:

The objectives of this application are to characterize the impact of radiation doses and qualities on retinal vasculature and tissue remodeling and to study the role of mitochondria in regulating oxidative stress-induced cellular damage and alteration of cell-cell interactions in the function of blood-retina-barrier (BRB). Archived ocular tissues samples at dose ranges from 0.1 Gy to 1 Gy with multiple particle types and energies across multiple animal species will be available for sharing from three NASA funded investigators. We will evaluate radiation –induced retinal vascular and tissue remodeling at multiple time points. Our study will elucidate the spectrum of radiation-induced structural and functional alteration in retinal BRB function and the mechanisms by which these

changes are mediated.


Specific Aim 1:
Define the relationships between radiation-induced oxidative stress in ROS expression, retinal vascular remodeling, and BRB function.
We will correlate cellular oxidative status with changes in retinal vascular topology, vascular endothelial cells (ECs), and BRB integrity using immunohistochemistry (IHC), stereological and automated image analyses, and magnetic resonance imaging diffusion tensor imaging (DTI-MRI). The observed changes in mice will be compared with that of rats and rabbits.

Specific Aim 2:
Determine whether radiation-induced oxidative damage in retina is mediated through photoreceptor mitochondrial ROS production. We will examine mitochondrial associated-oxidative stress and apoptosis and mitochondrial integrity in retinal photoreceptor using Western blot assays and histopathology.

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Mappings
RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
GapCBS-CNS - 1: Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?
GapCBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
GapCNS - 6: How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
You are here!TaskEffects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits

RiskRisk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
You are here!TaskEffects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits

RiskRisk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors
You are here!TaskEffects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits

RiskRisk of Spaceflight Associated Neuro-ocular Syndrome (SANS)
You are here!TaskEffects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits