Since all blood and lymph vessels are compliant, fluid-filled structures whose pressures are strongly influenced by gravity, we will focus on potential changes directly to the ocular vasculature caused by simulated microgravity. Therefore, the objective of this study is to determine whether the hindlimb unloading (HU) model of simulated microgravity causes a time-dependent change in structure and function of the ocular vasculature at the level of feed arteries, venous exchange vessels and lymph vessels, and whether sex differences influence these responses. The central hypothesis is that simulated microgravity causes temporal changes in structure/function of the ocular vasculature and subsequent alterations in ocular hydrodynamics leading to SANS.
These studies will provide a novel comprehensive evaluation of the temporal impact of simulated microgravity on ocular hydrodynamics in all the main microvascular compartments (feed arteries, veins and lymphatic vessels), and correlation of these findings with SANS. Outcomes will help identify the strengths and limitations of a murine HU model for SANS.
Control and HU groups of male and female mice will be studied. The ocular structure and function will be assessed after baseline, and 2 weeks and 4 weeks of HU or control conditions. We will use a systematic approach of in vivo and in vitro studies to assess artery, vein, and lymphatic vessel structure and function.
We will perform in vivo approaches to assess retinal microvascular structure and function using fundus imaging, Doppler ultrasound (central retinal artery flow velocity) and intravital imaging (microvascular permeability) in control and HU mice. Optical coherence tomography (OCT) imaging and histochemical staining of retinal tissue will also be performed for comprehensive evaluation of neural retina structure and function. In addition, neural retina function (a-wave and b-wave, and oscillatory potentials) will be assessed using the electroretinogram (ERG) and intraocular pressure will be measured with a tonometer.
To directly assess vascular function, ophthalmic arteries and ocular lymphatic vessels will be isolated and pressurized for in vitro studies of vascular reactivity. The immunohistochemical, molecular, and biochemical tools will be used to assess the impact of HU on the retinal microvascular tight junction proteins and levels of inflammatory cytokines in the retinal tissue. The outcomes from the vascular studies will be evaluated in relation to SANS symptoms and neural retina structure (OCT)/function (ERG).
This experiment is currently in progress. Results will be available at the conclusion of the study.
|Mission||Launch/Start Date||Landing/End Date||Duration|