Engineering topics

Shiyin Lim

Publications and source records attributed to Shiyin Lim.

3 records

NASA NTRSDate not supplied

Retinal Image Quality Assessment for Spaceflight-Induced Visual Impairment Study

Medical reports have identified visual impairments as a risk associated with extended exposure to microgravity. Etiology of these ocular changes is currently unknown. Current hypotheses propose cephalad fluid shifts resulting from microgravity as the primary cause of ocular damage. One approach to studying ocular response to microgravity is by examining possible changes in retinal blood vessels using a NASA model of microgravity, the head-down tilt (HDT) of human subjects undergoing prolonged bed rest (BR). Retinal vessels in astronauts and BR subjects are monitored by Heidelberg Spectralis infrared (IR) imaging, in which retinal image quality is limited by insufficient resolution of small vessels. Yet small vessels respond and remodel most actively to physiological stress.For our NASA study of BR subjects, we identify retinal image quality as thecapability to capture vascular detail to acceptable resolution of small vessels. We therefore are analyzing Spectralis images acquired with fluorescein angiography(FA), where increased contrast significantly improves image resolution. The FA images are of normal subjects participating in a clinical study on diabeticretinopathy (US National Institutes of Health). We hypothesize that FA Spectralis images are of superior quality compared to non-FA Spectralis IR images.

Rodrigo Rene Rai Munoz Abujder↗

NASA NTRSDate not supplied

Deletion of Cdkn1a in Mice Rescues Reduced Osteogenesis in Microgravity and Increases Coupled Osteoclastic Bone Degenerative Activity and Bone Loss

Elevated Cdkn1a/p21 levels in mouse bone during spaceflight have led us to hypothesize that this cell cycle inhibitor could regulate osteogenesis in response to mechanical unloading in microgravity. Cdkn1a interacts with cyclins CDK1/2/4,6 during G1 and S phases, and suppression of its expression by mechanical stretch enhances proliferation and mineralization in osteoblastic cell cultures. To test this hypothesis in a whole-organism model, we used C57BL/J6 WT/Cdkn1a-null mice in the NASA RR-10, 30-day ISS microgravity experiment. To quantify active mineralization in microgravity mice were injected with Calcein seven and two days before euthanasia on-orbit, followed by high-resolution confocal imaging of optically cleared femoral endosteal surfaces. To quantify cortical and cancellous bone parameters we conducted microCT analyses of the femur and tibia. Confocal imaging revealed a population of mineralizing calcein-positive single osteoblasts, and multicellular surfaces of mineralization by osteocytes in lacunae. The Cdkn1a-null genotype shows a greater ratio of early-osteoblasts to late-osteocytes and reduced mineralization versus WT. Additionally, in microgravity WT bones have a large (80%) decrease in active mineralization, but remarkably Cdkn1a deletion fully rescued mineralized surface loss. MicroCT shows trends for moderate spaceflight bone loss in WT femurs, and significant losses in the tibia, while Cdkn1a-null femurs showed much larger significant tissue losses, including 25% thinner trabeculae (p < 0.01),40% thinner cortical bone (p < 0.005), and 10% lower percent cortical bone area (p < 0.05). These results indicate that endogenous bone Cdkn1a plays a key role in mechanosensitive downregulation of osteoprecursor proliferation and promotes osteocytic differentiation. In microgravity however, while Cdkn1a deletion rescues mineralization, bone loss quantified by microCT is greatly increased, likely due to the molecular coupling of osteogenesis and osteoclastogenesis. This molecular mechanism opens the possibility for potential pharmacological approaches to mitigate bone loss in space simultaneously targeting Cdkn1a and osteoclast inhibition.

Eduardo A.C. Almeida↗

NASA NTRSDate not supplied

Murine Spine Composition and Mechanics are Maintained After 30-Days of Spaceflight

As NASA prepares to send astronauts on deep space missions, understanding the detrimental effects of spaceflight on the body is imperative. Spaceflight is known to negatively affect the spine, with astronauts experiencing systemic bone loss and increased post-flight risk of intervertebral disc herniation. Space investigations with rodent models have characterized some of the effects of spaceflight on the mammalian body, but variable experimental conditions have made it difficult to cohesively interpret results. These conditions include housing, flight duration, and for the spine, anatomical location. Thus, the objective of this study was to comprehensively characterize the effects of spaceflight on the bulk properties of the murine lumbar spine. To do this, we examined the lumbar spine of mice flown on the NASA Rodent Research 10 mission and analyzed disc biochemical content, disc joint material properties, lumbar vertebral body microarchitecture, and proximal tibia microarchitecture. Finally, we qualitatively examined bone growth in the vertebral bodies using confocal microscopy and on-orbit injections of calcein. Contrary to prior results, we found little to no effect of spaceflight on lumbar spine properties. Spaceflight, however, did negatively affect both cortical and trabecular bone properties of the proximal tibia load-bearing site. We hypothesize that this may be due to loading associated with increased physical activity in the second half of the mission, observed on in-flight videos, that reload the lumbar spine as mice utilize quadruped ambulation. This increased activity occurs after an initial period of relative inactivity in microgravity. In support of this hypothesis, we observed new L5 bone formation in the last seven days of spaceflight, suggesting that current 30-day experimental flight conditions may not be as effective at lumbar spine unloading as previous shorter flights.

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