Translaminar Autonomous System – a human ground-based analog

Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a significant unexplained adverse reaction to long-duration missions. We employ an ex vivo Translaminar Autonomous System to recreate a human ocular ground-based spaceflight analogue model to study SANS pathogenesis.
Translaminar Autonomous System – a human ground-based analog
Like

To the Moon, Mars, and Beyond –What are the consequences?

Prolonged exposure to microgravity can disrupt mechanisms of homeostasis and can change the pressure dynamics within the body. Long duration spaceflights further augment these detrimental mechanisms in astronauts, causing significant pathological changes within the central nervous system structures, including the eyes. Post-flight data of astronauts has depicted that ocular changes are observed in majority of space travelers during long term missions, and these can present as decreased distance and near visual acuity changes. Collectively these ocular changes have been termed as spaceflight associated neuro-ocular syndrome (SANS). The goal for this study was to use a novel human ground analog pressure model to simulate microgravity and produce the pathogenic effects of SANS. This will be particularly important as we plan long-term Moon, Mars and beyond missions.

Is there a human ocular analog for spaceflight associated neuro-ocular syndrome?

One factor implicated in SANS is elevated intracranial pressure, however, the mechanisms of damage due to this elevation around the optic nerve of the eye remains ambiguous. Prior to our novel Translaminar Autonomous System model, no other system could keep human eyes in culture for extended periods of time to study changes of translaminar pressure- the balance of pressure within (intraocular) and around the optic nerve (intracranial) of the eye. The model allows the autonomous regulation of both these pressures. Our team which included, Dr. Michael Peng, Stacy Curry, Dr. Yang Liu, Husain Lohawala, Gaurav Sharma and myself, Dr. Tasneem Putliwala Sharma, characterized this unique ground-based human eye analog to mimic aspects of SANS pathogenesis. We tested biochemical and functional assays using the human donor eyes to validate this model for future space studies.

Why is our research important

Currently, nearly 70% of astronauts on six month or longer missions have some form of SANS-related symptoms, including clinical findings and structural changes of globe flattening and visual hyperopic shifts. The structural change from SANS is thought to be brought about by pressure changes such as mildly elevated intracranial pressure. This mild elevation has been documented in astronauts’ post-flight. To understand this mechanism was of high interest to both our group and the Translational Research Institute for Space Health. The institute awarded us a research grant to study the impacts of various intraocular and intracranial pressures on the health of the eye, optic nerve, and retina cells. Using our model, we successfully maintained pressures under the various space simulations and tested the morphology of the eye under these conditions. We identified reduced axonal transport capacity, increased optic nerve degeneration, and retinal functional deficits. In addition, we documented identifiable pathogenic alterations in the human eyes by morphologic, apoptotic, and inflammatory assays under various simulated SANS conditions. Our results validated that our model could provide a potential unique preclinical application system to mimic SANS pathology and a viable therapeutic testing device for countermeasures.

What is the future impact of our studies?

These studies will address the critical need for investigation into ocular changes during spaceflight. This model will not only identify pathways of SANS pathogenesis, but also enable us to test countermeasures for astronauts to overcome this syndrome during long duration missions. Therapeutic countermeasures based on our mechanistic understanding of spaceflight-associated damage in the eye can alleviate or prevent vision changes that astronauts experience during long-duration spaceflights. We also hope to perform future work to identify if miRNA and mitochondrial damage pathways are activated due to microgravity in the eye and if there is a possible connection to SANS. We can even co-utilize other space stressors like radiation in our model to test the effects of multiple stressors on human eyes.  In conclusion, our model will address a major knowledge gap by simulating spaceflight stressors in human eye models to determine the causative agents of SANS and how they can be mitigated for long duration missions.

 

Please sign in or register for FREE

If you are a registered user on Microgravity Community, please sign in

Related Collections

With collections, you can get published faster and increase your visibility.

Human System Risk Management and Knowledge Graphs for Human Spaceflight

Human system risk in spaceflight through systematic processes and knowledge graphs developed at the NASA Human System Risk Board (HSRB).

Publishing Model: Open Access

Deadline: Ongoing