All Eyes on Space | Drug Discovery News

Astronauts on lengthy length missions in house usually develop a situation referred to as Spaceflight Related Neuro-ocular Syndrome (SANS) that results in blurry imaginative and prescient. Scientists are growing each space- and Earth-based programs to check the mechanisms underlying SANS and to develop remedies for it. These instruments received’t simply keep in house — they’ll assist within the prognosis and remedy of associated eye ailments for individuals right here on Earth.

Host: Stephanie DeMarco

Visitors:

A headshot of Prem Subramanian wearing a suit jacket and bow tie in front of a bookcase.

Prem Subramanian on the College of Colorado Anschutz

     Kjell Lindgren flies inside of the Kibo module on the International Space Station in 2015.

Kjell Lindgren at NASA

A photo of Andrew Lee wearing a dark suit jacket and tie standing in front of a wall of windows.

Andrew Lee on the Houston Methodist Hospital

  A headshot of Tasneem Sharma wearing a cream-colored blazer with black trim.

Tasneem Sharma on the Indiana College

Extra on this podcast:

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Transcript

Stephanie DeMarco: Hiya everybody, and welcome again to a brand new episode of DDN Dialogues! I’m your host, Stephanie DeMarco. At present’s story is, what you may name, a little bit bit — out of this world.

NASA Audio of Mercury 7 Mission: 5, 4, three, two, one, zero. [inaudible] Liftoff! The clock has began. Roger, loud and clear, Gus. Roger you look good down right here. Periscope is out. And now we have a go. Roger. Candy phrases [inaudible].

DeMarco: Think about: It’s the 12 months 2050, and also you’re hurtling by way of house on one of many first human missions to Mars. Over the course of months, you watch the Earth shrink right into a pale blue dot, wanting hardly totally different from the opposite stars throughout the inky blackness of house. 

However, because the months go by, you start to note that all the things seems to be rather less sharp than it did earlier than. There’s a blur in a specific spot in your imaginative and prescient, and now you end up squinting to learn the numbers on the ship’s devices. Hundreds of thousands of miles away from the closest eye physician, you’ve developed a situation fully distinctive to spaceflight referred to as Spaceflight-Related Neuro-ocular Syndrome or SANS.

Prem Subramanian: NASA has categorized SANS because the quantity two well being hazard limiting our means to do deep house exploration with primary being radiation publicity. So, it is clearly a very excessive precedence drawback to grasp and to unravel. The true concern is with a deep house exploration mission that would final for years that these modifications may preserve occurring, and worsen and worse, and ultimately result in imaginative and prescient loss within the midst of a mission.

DeMarco: That’s Prem Subramanian, a neuro-ophthalmologist on the College of Colorado Anschutz who research SANS. With firms like SpaceX and Blue Origin launching individuals into orbit and NASA’s Artemis missions to ship astronauts again to the Moon, we as people are venturing deeper into house and for longer durations of time than ever earlier than. That is placing house vacationers at greater danger of probably everlasting modifications to their imaginative and prescient.

However now, scientists are growing new space- and Earth-based instruments to check SANS and to check potential remedies for it. And whereas SANS could also be distinctive to spaceflight, these researchers are discovering that many of those new strategies can also result in new remedies for frequent eye circumstances right here on Earth.

Human beings — and all life on Earth — advanced within the presence of gravity. So, after we’re launched from its clutches, our our bodies go a little bit haywire. Bones lose density, muscle mass waste away with out train, and the immune system will get thrown fully out of whack. Kjell Lindgren, a NASA astronaut who has flown on two house missions and spent a little bit greater than 311 days in house, has firsthand expertise with many of those modifications.

Kjell Lindgren: The everyday modifications that we see with eyesight within the common crew member is that in case you did not want to make use of studying glasses on the bottom, you might have to make use of them on orbit. That meant, after I was engaged on a process, after I was studying electronic mail or after I’m doing upkeep or some exercise that is exact or nice that I usually wanted my glasses to have the ability to do this successfully. And, in fact, it is simple to misplace glasses on the bottom, it is even simpler to misplace them on orbit. So, I offered no finish of leisure to my youthful crew members, after I wanted assist discovering my glasses, and so I received an excellent quantity of ribbing for that as effectively.

DeMarco: I can’t even think about! You may’t precisely put them down wherever. They only type of float away.

Lindgren: For awhile there, we have been we have been right down to our our final pair, and so they needed to to resort to some drastic measures to ensure I’d be capable of discover these if I wanted to.

DeMarco: So, whereas short-term imaginative and prescient modifications are simply one other bizarre factor that occurs to the physique in house, researchers seen that as extra astronauts returned from longer missions, they got here again with extra extreme modifications to their imaginative and prescient.

Lindgren: The problems popped up when a few of our crew members within the 2000s skilled extra everlasting or longer-term visible modifications. That is actually what kicked this investigation off to try to perceive the etiology of the underlying points that have been contributing to those visible modifications. What we thought have been acute and non permanent visible modifications for a very long time, now acknowledge to perhaps be a part of this bigger continuum of SANS.

Subramanian: Within the late 2000s, we began to note that some lengthy length spaceflight astronauts have been having swelling of their optic nerves, after which in 2011, a extra complete report about this was printed. 

DeMarco: In that report, scientists famous that along with optic nerve swelling, one of many clearest modifications in astronauts’ eyes happened within the choroid, the blood vessel crammed layer of the attention that sits simply behind the retina and in entrance of the again wall of the attention.

Subramanian: That choroid swells. It turns into thicker than it’s in a terrestrial setting, and that choroidal swelling will be related to some change within the refractive error of the attention. It makes individuals a little bit bit farsighted, makes it more durable to focus at close to.

DeMarco: Why the choroid and the optic nerve swells, although, remains to be unclear. However scientists’ prime suspect is the lack of gravity. Andrew Lee, a neuro-opthalmologist at Houston Methodist Hospital advised me extra.

Andrew Lee: The exact mechanism of SANS is unknown. Nonetheless, it’s believed to be microgravity. So fluid, which usually could be pulled down in the direction of your ft, will get caught upstairs — each in your head and within the orbit.

DeMarco: In truth, scientists have noticed that when strain within the head will increase in sure circumstances on Earth, individuals have comparable modifications to their imaginative and prescient.

Subramanian: When SANS was first acknowledged, it was referred to as VIIP: Imaginative and prescient Impairment Intracranial Stress syndrome as a result of the optic nerve swelling that was seen was regarded as similar to the elevated strain dysfunction on Earth referred to as Idiopathic Intracranial Hypertension. Now that we have discovered extra about SANS, we all know it might not be fairly the identical, however there are some options that they share. Sufferers with IIH get swelling of their optic nerves. They’ve excessive strain of their head. That swelling of their optic nerves can result in visible disturbances, even imaginative and prescient loss.  

Lee: There are different proposed mechanisms, nevertheless, together with metabolic issues, and it isn’t clear whether or not the fluid is just within the orbit or within the head as effectively, inflicting elevated intracranial strain. So, there are a number of different fluid dynamic issues that could possibly be at play. One of the best countermeasure that now we have for SANS is simply to return to Earth and return to our gravitational discipline.

DeMarco: But when astronauts are months away from Earth, merely coming again house received’t clear up the issue. And generally, even returning to Earth’s gravity doesn’t make things better both.

Subramanian: There was not less than one astronaut who had persistent swelling of the optic nerve for not less than 20 months after returning to the terrestrial setting, and we nonetheless don’t know precisely why it endured that lengthy. Additionally, that choroid layer can develop some irregularity inside it that we are able to see after we look within the eye as a fold, and people folds can generally persist as effectively.

DeMarco: One of the simplest ways to check a situation that’s distinctive to spaceflight looks as if it could be in house. However, sending scientists as much as house isn’t precisely cost-effective or possible. However, that’s to not say that nothing will be completed in house.

Lindgren: We have got a remarkably strong analysis program, together with a number of the means to picture the attention each on the bottom and in house. We use ocular coherence tomography which offers simply a completely superb view of the layers of the again of the attention — actually the layers which might be most affected by a number of the SANS modifications, and so we’re wanting on the choroid and the retina even through the flight, we’re capable of monitor the crew’s anatomic modifications in addition to visible acuity by way of the testing that we do.

DeMarco:  Lee, Subramanian, and different researchers are growing new instruments to raised perceive the mechanisms of SANS instantly in house. For Subramanian, that appears like a little bit like a contact lens.

Subramanian: We’re working with SpaceX astronauts occurring the Polaris Daybreak mission, who’re going to be carrying a particular contact lens that measures the strain within the eye, the intraocular strain, and measures it consistently over the course of hours to offer us a greater understanding as a result of there could also be some type of relationship between modifications in eye strain and what’s occurring with the optic nerve swelling. So, we’re additionally going to measure the size of their eye as a result of that tells us one thing about swelling in that choroid. 

DeMarco: Lee has additionally give you a wearable method to monitor SANS in house.

Lee: Area is a commodity in house, so it takes some huge cash simply to ship one thing up there. And the quantity of obtainable actual property that now we have on the Worldwide Area Station may be very small, so we will not be sending large machines. We actually wish to have one thing that is moveable, ideally wearable head mounted, and so the units that we have been engaged on are head mounted goggle-based shows the place the sorts of exams that we’re doing — the visible acuity, the visible discipline, testing the distinction — could possibly be generated within a goggle. 

DeMarco: Lee has already began testing this system on wholesome members and located that it’s user-friendly, secure, and handy for individuals to make use of. He and his workforce are actually engaged on integrating it with an interactive, synthetic intelligence part. AI might be vital particularly for testing and diagnosing SANS on long-term house missions.

Lee: The journey to Mars is so lengthy — 15 months spherical journey. Ideally, we’d have units that will acquire all the information in a short time, after which we may analyze it in actual time. In fact, there is a delay within the sign the additional and additional you might be away, so the interactive part could possibly be doubtlessly AI pushed in order that the physician would not truly should be speaking to the astronaut in actual time, particularly when that type of dialog could be 20 minutes earlier than you get the reply as a result of it is simply so distant. This expertise has each terrestrial and extra-terrestrial functions. We hope to develop the system each for testing of SANS, however for testing of different circumstances that will enhance the lives of individuals right here on earth as effectively.

DeMarco: Whereas units that monitor astronauts’ eyes throughout spaceflight will undoubtedly assist researchers perceive SANS higher, cleverly-designed Earth-based methods have potential too.

Subramanian: A method is by astronauts once they come again from lengthy length spaceflight and learning what they appear to be once they return to Earth in comparison with what they seemed like once they went, and what I imply by that’s you are able to do issues like MRI scans even of their brains to search for attribute modifications that may happen due to shifts in physique fluids and publicity to that microgravity setting.

There may be an analogue of microgravity that has been developed, the place persons are assigned to strict bedrest mendacity on their backs and tilted six levels head down, so to imitate that pooling of fluid towards the pinnacle. And that six diploma head down tilt mannequin has been fairly profitable in reproducing some, however not all, of the modifications that occur when astronauts are in true spaceflight, and the variations truly between what occurs in that experimental mannequin and what occurs in actual spaceflight may very well train us one thing about what’s inflicting a few of these issues.

DeMarco: These strategies have improved researchers’ information of what occurs to astronauts throughout spaceflight, however scientists nonetheless need a method to examine how particular pressures in each the pinnacle and the attention contribute to SANS. A brand new technique got here from Tasneem Sharma, an ophthalmology researcher at Indiana College, who was initially in search of a method to research and take a look at remedies for glaucoma.

Tasneem Sharma: So, glaucoma is a illness that’s prevalent. Virtually 70 million individuals endure as a result of illness worldwide, and some of the or main danger elements for glaucoma is elevated strain throughout the eye.

DeMarco: In glaucoma, the optic nerve turns into broken, which results in progressive and incurable imaginative and prescient loss. Sharma received her begin working in tissue engineering and stem cells. And through her postdoctoral analysis, she differentiated pores and skin fibroblasts into stem cells, which she then differentiated into human retinal neurons. She and her colleagues may then take a look at potential glaucoma remedies on these newly shaped retinal neurons.

Sharma: We have now stem cells. We have now glaucoma, and now we have all these mouse fashions. However there may be not a human mannequin system that we are able to research all of this in, and that is what sort of gave start to the mannequin, which is the Translaminar Autonomous System.

DeMarco: To review human eyes within the Translaminar Autonomous System — or TAS for brief — Sharma and her workforce take a donor human eye and reduce it down the equator, bisecting the attention with the lens and the iris on one aspect and the again of the attention and the optic nerve on the opposite. She and her workforce then place the again half of the attention face-down on prime of a 3D-printed dome construction within the backside a part of the TAS chamber. This fashion the optic nerve factors upward. They place a lid on prime of the underside chamber and use fluid flowing at totally different charges to set a particular strain in every chamber.

Sharma: It consistently measures strain inside that prime chamber the place the nerve is, and the chamber which is inside to the attention. We are able to type of mimic and modulate a few of these strain dynamics within the human eye, so we are able to take a look at how this eye would react below excessive and low strain circumstances to imitate the pathophysiology of glaucoma. After which if we put in a drug, would that assist the cells or the retinal neurons survive higher?

DeMarco: She and her workforce began making use of for funding to proceed her analysis utilizing this new system.

Sharma: I had type of emailed a few totally different funding companies right here and there. One of many funding companies that I had you already know simply despatched a paragraph about my mannequin to was Translational Analysis Institute for Area Well being. Emmanuel Urquieta, he referred to as and he is like, “this can be a very novel mannequin. Astronauts once they go into house flight, over lengthy length house missions of greater than six months, virtually 70% of them see some type of visible defects, and that is termed now as Spaceflight-Related Neuro-ocular Syndrome. So we see hyperopic shifts in eye, principally. As a result of there may be circumstances of microgravity, all of the fluid within the physique shifts to the mind, and that really causes strain on the attention. And will we use your system to characterize a few of these results? So, why do not you apply for this grant? And, if we prefer it, we are going to fund you.” And, that is what occurred.

DeMarco: So, Sharma and her workforce arrange their TAS to check donor human eyes below a variety of various intraocular and intracranial pressures that astronauts are thought to expertise below microgravity circumstances.

Sharma: We have been actually excited. We wished to do a 14-day research and a 30-day research, after which COVID hit, and when COVID hit, all of the human eyes that began coming into the lab have been COVID optimistic, and we could not settle for them anymore. So, we needed to actually streamline our challenge and publish with the smaller pattern cohort that we had. However even in that small pattern cohort, we have been actually amazed by the type of trajectory and the tendencies that we’re seeing: that there’s a risk that strain dynamics across the nerve and inside the attention could possibly be making modifications, and that the astronauts over lengthy length house missions could possibly be having imaginative and prescient defects.

DeMarco: They noticed that whereas the general form of the again of the attention remained the identical below these spaceflight-like pressures, there have been main modifications on the molecular stage. Once they analyzed gene expression in peripheral retinal tissue, the researchers noticed elevated expression of genes concerned in irritation and apoptosis. They then remoted the optic nerves from these eyes. And, in the entire microgravity-modeled strain circumstances, they noticed clear degeneration of the optic nerve axons.

Sharma: One of many issues that occurs attributable to this strain dynamics in microgravity for these astronauts is the nerve that connects the attention to the mind additionally turns into torturous or kinks. And we noticed that when this kinking occurs, it will increase the degeneration within the eye. That was a proof of idea for us, in order that was actually fascinating additionally data-wise.

DeMarco: Now that she has a method to mannequin SANS in an ex vivo system on Earth, Sharma desires to raised characterize SANS and to make use of TAS to start testing potential therapeutics.

Sharma: Proper now, strain isn’t the one speculation for Spaceflight-Related Neuro-ocular Syndrome. Hypothetically, there could possibly be elevated carbon dioxide ranges, salt food regimen, totally different one carbon metabolism pathways, venous blood strain mechanism, venous circulation strain mechanisms, all these different pathways that could possibly be inflicting the SANS to be growing.

Possibly there may be elevated intracranial strain due to the fluid shifts, and that is what’s inflicting this. So, our mannequin permits us to type of tease that out. It doesn’t say that, okay, all the opposite pathways are usually not part of it, however the large query is, is that elevated intracranial strain, is {that a} pathogenic occasion? From the tendencies that we noticed with our knowledge, there may be the likelihood that could be a pathogenic occasion we have to discover that additional for astronauts.

Lindgren: We’re actually grateful that the human analysis neighborhood has stepped as much as assist us determine and characterize this course of. As we go additional away from the Earth, deeper into the photo voltaic system, for longer durations of time, it is one thing that we have to really totally perceive in order that we are able to hopefully mitigate these modifications and reduce the danger of everlasting modifications in eye well being.

Lee: SANS is thrilling and fascinating to me as a neuro-ophthalmologist only for the neuro ocular structural findings that we see. Nonetheless, by way of an even bigger image, it is deeply ingrained within the human spirit to wish to discover, and that exploration will be an inside exploration of our our bodies and our minds or an outer exploration into the mysteries of house and the origins of our universe. And, and in spite of everything, that is what science is: exploration. So, for me to take part within the manned spaceflight program, even when the participation is only a small a part of the attention, may be very thrilling.

DeMarco: That’s it for this episode of DDN Dialogues. Thanks to Prem Subramanian, Kjell Lindgren, Andrew Lee, and Tasneem Sharma for speaking with me for this episode, and thanks a lot for listening! Till subsequent time, I’m your host Stephanie DeMarco. 

This episode of DDN Dialogues was reported, written, and edited by me, with further audio modifying by Jessica Good. To by no means miss an episode, subscribe to DDN Dialogues wherever you get your podcasts.

And, the following time you search for on the night time sky, consider simply what number of pairs of glasses are floating across the Worldwide Area Station, serving to human beings see the secrets and techniques of the universe a little bit extra clearly.

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