Task Effects of low-dose radiation on neurovascular remodeling and blood-retina barrier function in mice, rats and rabbits
Last Published:  11/23/20 11:55:12 AM (Central)
Short Title: Tissue Sharing Flagship
Responsible HRP Element: Human Health Countermeasures
Collaborating Org(s):
Space Radiation (SR) Element
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):

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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