Task Head-down tilt as a model for intracranial and intraocular pressures, and retinal changes during spaceflight (Fuller)
Last Published:  07/30/21 01:05:34 PM (Central)
Short Title: Rodent model for VIIP - Fuller
Responsible HRP Element: Human Health Countermeasures
Collaborating Org(s):
Human Health Countermeasures (HHC) Element
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
Aims:
To determine if the cephalic fluid shift seen during microgravity exposure is the causative factor leading to the ocular changes seen in astronauts after long-term space flight (Watkins and Barr 2010) (Mader, Gibson et al. 2011). The Hind Limb Suspended (HLS) rat model of microgravity will be used to answer the following specific aims. The HLS rat model will allow us to approach these questions and more rapidly achieve the program objectives. A 90-day suspension experiment utilizing the rat model, which we have performed numerous times, is roughly equivalent to a 2.5-year exploration class mission, or bedrest study, in a human subject based on lifespans.

Specific Aim 1. To determine if the microgravity model of rat hindlimb suspension (HLS)
results in increased intracranial (IOP) and intraocular (IOP) pressures, as well as alterations in ophthalmic anatomy and/or function.

In order to answer this specific aim, we will test the following hypotheses:

Hypothesis 1a. HLS male rats will have a higher ICP and IOP than control male rats. Further, the HLS male rats will have altered ophthalmic morphology and function including, but not limited to, flattening of the globe, increased diameter of the optic nerve and alterations in retinal function.
Hypothesis 1b. Post-suspension, ICP and IOP will return to pre-suspension levels and ophthalmic morphology and function will also recover over time.

Specific Aim 2. To determine if there is a gender differences in the ophthalmic responses to increased ICP and IOP.

In order to answer this specific aim, we will test the following hypotheses:

2a. HLS will results in increased ICP, IOP and altered ophthalmic features in female animals compared to female controls, but the responses will not be different from HLS males studied in
Specific Aim 1.
2b. Post-suspension recovery of ICP, IOP and ophthalmic features in female rats will not have a longer time course compared to the HLS males of Specific Aim 1.

Specific Aim 3. To determine if aging increases the ophthalmic responses to increased ICP and IOP.

In order to answer this specific aim, we will test the following hypotheses:

3a. The effects of HLS on ICP, IOP and ophthalmic features will be greater in older animals compared to both age-matched controls and the younger HLS males of Specific Aim 1.
3b. Post-suspension recovery of ICP, IOP and ophthalmic features will have a longer time course in older rats compared to the younger HLS males of Specific Aim 1.

Specific Aim 4. To determine if elevated atmospheric carbon dioxide (CO2) levels affect the ophthalmic responses to increased ICP and IOP in male rats.

In order to answer this specific aim, we will test the following hypotheses:

4a. The effects of HLS in young male rats on ICP, IOP and ophthalmic features will be increased in a mildly hypercapnic environment compared both to hypercapnic controls and the HLS males of Specific Aim 1 in room air.

4b. Post-suspension recovery of ICP, IOP and ophthalmic features in young male rats will have a longer time course in male rats simultaneously exposed to HLS and increased CO2 levels, compared to controls and the recovery of HLS males in Specific Aim 1 in room air.

This study combines two studies from the 2011 NRA: C. Fuller and S. Zanello.
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