Science
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Cellular Mechanism for Severe Viral Hepatitis Identified
(Professor Shin(left) and Professor Jung)
KAIST medical scientists identified a cellular mechanism causing inflammatory changes in regulatory T cells that can lead to severe viral hepatitis. Research on this mechanism will help further understand the nature of various inflammatory diseases and lead to the development of relevant clinical treatments.
It is known that activated immune cells of patients with viral hepatitis destroy hepatocyte, but its regulatory mechanism has not yet been described.
Regulatory T cells inhibit activation of other immune cells and thus are important for homeostasis of the immune system. However, recent studies contradictorily show that immune inhibitory functions of regulatory T cells weaken in inflammatory conditions and the cells secrete inflammatory cytokines in response. Meanwhile, such a phenomenon was not observed in viral hepatitis including types A, B and C.
The team focused on changes in regulatory T cells in patients with viral hepatitis and discovered that regulatory T cells undergo inflammatory changes to secrete inflammatory cytokines (protein secreted by immune cells) called TNF. They also proved regulatory T cells that secrete TNF contribute to the progression of viral hepatitis.
The team confirmed that regulatory T cells of acute hepatitis A patients have reduced immune-inhibitory functions. Instead, their regulatory T cells secrete TNF. Through this research, the team identified a molecular mechanism for changes in regulatory T cells and identified the transcription factor regulating the process. Furthermore, the team found similar changes to be also present in hepatitis B and C patients.
A KAIST immunology research team led by Professors Eui-Cheol Shin and Min Kyung Jung at the Graduate School of Medical Science & Engineering conducted this translational research with teams from Chungnam National University and Yonsei University to identify the mechanism in humans, instead of using animal models. The research was described in Gastroenterology last December.
Professor Shin said, “This is the first research on regulatory T cells that contributes to hepatocyte damage in viral hepatitis.” He continued, “It is significant for identifying the cells and the molecules that can be used as effective treatment targets for viral hepatitis in the future. This research was funded by the Samsung Science and Technology Foundation.
(Figure1: Treg cells from acute hepatitis A (AHA) patients produce tumor necrosis factor (TNF) andhave reduced suppressive activity. These changes are due to a decrease in FoxP3 transcription factor and an increase in RORγt transcription factor. TNF-producing Treg cells are associated with severe liver injury in AHA patients.)
(Figure 2: A higher proportion of Treg cells from patients with acute hepatitis A, compared with healthy controls, produced TNF upon stimulation with anti-CD3 and anti-CD2. This study reports the presence and the significance of TNF-producing Treg cells for the first time in human patients.)
2018.01.18 View 7762 -
Lifespan of Fuel Cells Maximized Using Small Amount of Metals
(Professor Jung (far right) and his team)
Fuel cells are key future energy technology that is emerging as eco-friendly and renewable energy sources. In particular, solid oxide fuel cells composed of ceramic materials gain increasing attention for their ability to directly convert various forms of fuel such as biomass, LNG, and LPG to electric energy.
KAIST researchers described a new technique to improve chemical stability of electrode materials which can extend the lifespan by employing a very little amount of metals.
The core factor that determines the performance of solid oxide fuel cells is the cathode at which the reduction reaction of oxygen occurs. Conventionally, oxides with perovskite structure (ABO3) are used in cathodes. However, despite the high performance of perovskite oxides at initial operation, the performance decreases with time, limiting their long-term use. In particular, the condition of high temperature oxidation state required for cathode operation leads to surface segregation phenomenon, in which second phases such as strontium oxide (SrOx) accumulate on the surface of oxides, resulting in decrease in electrode performance. The detailed mechanism of this phenomenon and a way to effectively inhibit it has not been suggested.
Using computational chemistry and experimental data, Professor WooChul Jung’s team at the Department of Materials Science and Engineering observed that local compressive states around the Sr atoms in a perovskite electrode lattice weakened the Sr-O bond strength, which in turn promote strontium segregation. The team identified local changes in strain distribution in perovskite oxide as the main cause of segregation on strontium surface. Based on these findings, the team doped different sizes of metals in oxides to control the extent of lattice strain in cathode material and effectively inhibited strontium segregation.
Professor Jung said, “This technology can be implemented by adding a small amount of metal atoms during material synthesis, without any additional process.” He continued, “I hope this technology will be useful in developing high-durable perovskite oxide electrode in the future.”
The study co-led by Professor Jung and Professor Jeong Woo Han at Department of Chemical Engineering, University of Seoul was featured as the cover of Energy and Environmental Science in the first issue of 2018.
(Figure1.Correlation between the extent of lattice strain in electrode, strontium segregation, and electrode reaction.)
(Figure 2. Cathode surface of solid oxide fuel cell stabilized using the developed technology)
2018.01.18 View 7427 -
KAIST Students Invited to the BNL
Siheon Ryee and Taek Jung Kim, combined Masters and PhD students from the Department of Physics, have been invited to be visiting researchers at the Brookhaven National Laboratory (BNL).
The BNL, located in Long Island, New York, is one of the most esteemed institutes in the United States. Ryee and Kim received the invitation from the Center for Computational Design of Functional Strongly Correlated Materials and Theoretical Spectroscopy. This center was established by scholars who have been leading this field in the United States.
The two students will be participating in developing a methodology and code for calculating strongly correlated electronic materials, and a grant of 40,000 USD will be provided to each student. This amount of support is not often awarded to researchers outside of postdoctoral programs.
Moreover, they are guaranteed to continue their combined Masters and PhD program and write their dissertations under the supervision of their advisor, Professor Myung Joon Han from the Department of Physics.
Professor Han said, “I was impressed by how well-known scholars established the center in order to cooperate with each other to solve challenging problems. Also, I was surprised and happy that my students were invited to this outstanding institute.”
“I believe that doing research with leaders in their field will give valuable experience to the students. At the same time, my students will be a great help to the scholars of the institute,” he added.
2018.01.11 View 6656 -
Meet the KAISTian of 2017, Professor YongKeun Park
Professor YongKeun Park from the Department of Physics is one of the star professors in KAIST. Rising to the academic stardom, Professor Park’s daily schedule is filled with series of business meetings in addition to lab meetings and lectures.
The year 2017 must have been special for him. During the year, he published numerous papers in international journals, such as Nature Photonics, Nature Communications and Science Advances. These high performances drew international attention from renowned media, including Newsweek and Forbes. Moreover, recognizing his research performance, he was elected as a fellow member of the Optical Society (OSA) in his mid-30s. Noting that the members’ age ranges from late 50s to early 60s, Professor Park’s case considered to be quite exceptional.
Adding to his academic achievement, he has launched two startups powered of his own technologies. One is called Tomocube, a company specialized in 3-D imaging microscope using holotomography technology. His company is currently exporting the products to multiple countries, including the United States and Japan. The other one is The.Wave.Talk which has technologies for examining pre-existing bacteria anywhere and anytime.
His research career and entrepreneurship are well deserved recipient of many honors. At the 2018 kick-off ceremony, Professor Park was awarded the KAISTian of 2017 in recognition of his developing holographic measure and control technology as well as founding a new field for technology application.
KAISTian of the Year, first presented in 2001, is an award to recognize the achievements and exemplary contribution of KAIST member who has put significant effort nationally and internationally, enhancing the value of KAIST.
While receiving the award, he thanked his colleagues and his students who have achieved this far together. He said, “I would like to thank KAIST for providing environment for young professors like me so that we can engage themselves in research. Also, I would like to mention that I am an idea seeder and my students do the most of the research. So, I appreciate my students for their hard works, and it is very pleasure to have them. Lastly, I thank the professors for teaching these outstanding students. I feel great responsibility over this title. I will dedicate myself to make further progress in commercializing technology in KAIST.”
Expecting his successful startup cases as a model and great inspiration to students as well as professors, KAIST interviewed Professor Park.
Q What made you decide to found your startups?
A I believed that my research areas could be further used. As a professor, I believe that it is a university’s role to create added value through commercializing technology and creating startups.
Q You have co-founded two startups. What is your role in each company?
A So, basically I have two full-time jobs, professor in KAIST and CTO in Tomocube. After transferring the technology, I hold the position of advisor in The.Wave.Talk.
(Holographic images captured by the product Professor Park developed)
Q Do your students also participate in your companies or can they?
A No, the school and companies are separate spaces; in other words, they are not participating in my companies. They have trained my employees when transferring the technologies, but they are not directly working for the companies.
However, they can participate if they want to. If there’s a need to develop a certain technology, an industry-academia contract can be made. According to the agreement, students can work for the companies.
Q Were there any hardships when preparing the startups?
A At the initial stage, I did not have a financial problem, thanks to support from Startup KAIST. Yet, inviting capital is the beginning, and I think every step I made to operate, generate revenue, and so on is not easy.
Q Do you believe KAIST is startup-friendly?
A Yes, there’s no school like KAIST in Korea and any other country. Besides various programs to support startup activities, Startup KAIST has many professors equipped with a great deal of experience. Therefore, I believe that KAIST provides an excellent environment for both students and professors to create startups.
Q Do you have any suggestion to KAIST institutionally?
A Well, I would like to make a comment to students and professors in KAIST. I strongly recommend them to challenge themselves by launching startups if they have good ideas. Many students wish to begin their jobs in government-funded research institutes or major corporates, but I believe that engaging in a startup company will also give them valuable and very productive experience.
Unlike before, startup institutions are well established, so attracting good capital is not so hard. There are various activities offered by Startup KAIST, so it’s worthwhile giving it a try.
Q What is your goal for 2018 as a professor and entrepreneur?
A I don’t have a grand plan, but I will work harder to produce good students with new topics in KAIST while adding power to my companies to grow bigger.
By Se Yi Kim from the PR Office
2018.01.03 View 9917 -
A Glance at the 2017 KAIST Literary Awards Ceremony
Since KAIST is a university specializing in science and engineering, people may think that the students rarely engage in literary activities. But KAIST students also excel in writing literature.
The 23rd KAIST Literary Award Ceremony was held on December 14 on the KAIST main campus. The award was established in 1995 to encourage students’ creative activities and to promote literary attainment. It is open to all KAIST students from undergraduate to masters and PhD students. This year, 43 students submitted a total of 68 literary works in the genres of poetry, novel, critique, and scenario.
KAIST professors Dong Ju Kim, Bong Gwan Jun, and Yunjeong Jo from the School of Humanities & Social Sciences participated as judges for the awards and they were joined by writers from the 8th Endless Road Program who served as invited judges for the novels and scenarios.
The Endless Road Program is a KAIST project for supporting artists who are engaged in literary works including scenarios, novels, webtoons, and movies by providing residences and funds. Novelists Jin Young Choi and Hak Chan Kim participated as judges for the novels and a drama scriptwriter, Joo Kim, as a judge of the scenarios.
After thorough evaluation, four submissions were chosen as awardees.
Section
Award
Name
Poetry
Winner
Sung Gil Moon (PhD candidate from the College of Business)
Runner-up
Jong Ik Jeon (Undergraduate student)
Novel
Winner
Joo Hwan Kim
(Undergraduate from the Dept. of Chemical and Biomolecular Engineering)
Runner-up
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Essay & Critique
Winner
-
Runner-up
Jung Joon Park
(PhD candidate from the Dept. of Bio and Brain Engineering)
Scenario
Winner
-
Runner-up
-
The literary works as well as a review of the awards will be published in the KAIST Times in 2018.
2017.12.15 View 6821 -
A New Spin Current Generating Material Developed
(Professor Park(left) and Ph.D. candidate Kim)
Magnetic random-access memory (MRAM) is a non-volatile device made of thin magnetic film that can maintain information without an external power supply, in contrast to conventional silicon-based semiconductor memory. It also has the potential for high-density integration and high-speed operation.
The operation of MRAM involves the control of the magnetization direction by exerting spin current-induced torque on a magnetic material. Spin current is generated using electricity in conventional MRAM, but this study developed materials technology that generates spin current using heat.
A KAIST research team led by Professor Byong-Guk Park of the Department of Materials Science and Engineering developed a material that generates spin current from heat, which can be utilized for a new operation principle for MRAM.
There have been theoretical reports on the spin Nernst effect, the phenomenon of the thermal generation of spin current, but is yet to have been experimentally proven due to technological limitations. However, the research team introduced a spin Nernst magnetoresistance measurement method using tungsten (W) and platinum (Pt) with high spin orbit coupling which allows for the experimental identification of the spin Nernst effect. They also demonstrated that the efficiency of spin current generation from heat is similar to that of spin current generated from electricity.
Professor Park said, “This research has great significance in experimentally proving spin current generation from heat, a new physical phenomenon. We aim to develop the technology as a new operational method for MRAM through further research. This can lower power consumption, and is expected to contribute to the advancement of electronics requiring low power requirement such as wearable, mobile, and IOT devices”.
This research was conducted as a joint research project with Professor Kyung-Jin Lee at Korea University and Professor Jong-Ryul Jeong at Chungnam National University. It was published in Nature Communications online on November 9 titled “Observation of transverse spin Nernst magnetoresistance induced by thermal spin current in ferromagnet/non-magnet bilayers.” Ph.D. candidate Dong-Jun Kim at KAIST is the first author. This research was funded by the Ministry of Science and ICT.
(Schematic diagram of spin Nernst magnetoresistance)
(Research result of new spin current generating materials)
2017.12.08 View 7275 -
Professor YongKeun Park Elected as a Fellow of the Optical Society
Professor YongKeun Park, from the Department of Physics at KAIST, was elected as a fellow member of the Optical Society (OSA) in Washington, D.C. on September 12. Fellow membership is given to members who have made a significant contribution to the advancement of optics and photonics.
Professor Park was recognized for his research on digital holography and wavefront control technology.
Professor Park has been producing outstanding research outcomes in the field of holographic technology and light scattering control since joining KAIST in 2010. In particular, he developed and commercialized technology for a holographic telescope. He applied it to various medical and biological research projects, leading the field worldwide.
In the past, cells needed to be dyed with fluorescent materials to capture a 3-D image. However, Professor Park’s holotomography (HT) technology can capture 3-D images of living cells and tissues in real time without color dyeing. This technology allows diversified research in the biological and medical field.
Professor Park established a company, Tomocube, Inc. in 2015 to commercialize the technology. In 2016, he received funding from SoftBank Ventures and Hanmi Pharmaceutical. Currently, major institutes, including MIT, the University of Pittsburgh, the German Cancer Research Center, and Seoul National University Hospital are using his equipment.
Recently, Professor Park and his team developed technology based on light scattering measurements. With this technology, they established a company called The Wave Talk and received funding from various organizations, such as NAVER. Its first product is about to be released.
Professor Park said, “I am glad to become a fellow member based on the research outcomes I produced since I was appointed as a professor at KAIST. I would like to thank the excellent researchers as well as the school for its support. I will devote myself to continuously producing novel outcomes in both basic and applied fields.”
Professor Park has published nearly 100 papers in renowned journals including Nature Photonics, Nature Communications, Science Advances, and Physical Review Letters.
2017.10.18 View 10193 -
Ultra-Fast and Ultra-Sensitive Hydrogen Sensor
(From left: Professor Kim, Ph.D. candidate Koo, and Professor Penner)
A KAIST team made an ultra-fast hydrogen sensor that can detect hydrogen gas levels under 1% in less than seven seconds. The sensor also can detect hundreds of parts per million levels of hydrogen gas within 60 seconds at room temperature.
A research group under Professor Il-Doo Kim in the Department of Materials Science and Engineering at KAIST, in collaboration with Professor Reginald M. Penner of the University of California-Irvine, has developed an ultra-fast hydrogen gas detection system based on a palladium (Pd) nanowire array coated with a metal-organic framework (MOF).
Hydrogen has been regarded as an eco-friendly next-generation energy source. However, it is a flammable gas that can explode even with a small spark. For safety, the lower explosion limit for hydrogen gas is 4 vol% so sensors should be able to detect the colorless and odorless hydrogen molecule quickly. The importance of sensors capable of rapidly detecting colorless and odorless hydrogen gas has been emphasized in recent guidelines issued by the U.S. Department of Energy. According to the guidelines, hydrogen sensors should detect 1 vol% of hydrogen in air in less than 60 seconds for adequate response and recovery times.
To overcome the limitations of Pd-based hydrogen sensors, the research team introduced a MOF layer on top of a Pd nanowire array. Lithographically patterned Pd nanowires were simply overcoated with a Zn-based zeolite imidazole framework (ZIF-8) layer composed of Zn ions and organic ligands. ZIF-8 film is easily coated on Pd nanowires by simple dipping (for 2–6 hours) in a methanol solution including Zn (NO3)2·6H2O and 2-methylimidazole.
(This cover image depicts lithographically-patterned Pd nanowires overcoated with a Zn-based zeolite imidazole framework (ZIF-8) layer.)
As synthesized ZIF-8 is a highly porous material composed of a number of micro-pores of 0.34 nm and 1.16 nm, hydrogen gas with a kinetic diameter of 0.289 nm can easily penetrate inside the ZIF-8 membrane, while large molecules (> 0.34 nm) are effectively screened by the MOF filter. Thus, the ZIF-8 filter on the Pd nanowires allows the predominant penetration of hydrogen molecules, leading to the acceleration of Pd-based H2 sensors with a 20-fold faster recovery and response speed compared to pristine Pd nanowires at room temperature.
Professor Kim expects that the ultra-fast hydrogen sensor can be useful for the prevention of explosion accidents caused by the leakage of hydrogen gas. In addition, he expects that other harmful gases in the air can be accurately detected through effective nano-filtration by using of a variety of MOF layers.
This study was carried out by Ph.D. candidate Won-Tae Koo (first author), Professor Kim (co-corresponding author), and Professor Penner (co-corresponding author). The study has been published in the online edition of ACS Nano, as the cover-featured image for the September issue.
Figure 1. Representative image for this paper published in ACS Nano, August, 18.
Figure 2. Images of Pd nanowire array-based hydrogen sensors, scanning electron microscopy image of a Pd nanowire covered by a metal-organic framework layer, and the hydrogen sensing properties of the sensors.
Figure 3. Schematic illustration of a metal-organic framework (MOF). The MOF, consisting of metal ions and organic ligands, is a highly porous material with an ultrahigh surface area. The various structures of MOFs can be synthesized depending on the kinds of metal ions and organic ligands.
2017.09.28 View 10015 -
Photoacoustic Imaging and Photothermal Cancer Therapy Using BR Nanoparticles
(Professor Sangyong Jon and PhD Candidate Dong Yun Lee)
Sangyong Jon, a professor in the Department of Biological Sciences at KAIST, and his team developed combined photoacoustic imaging and photothermal therapy for cancer by using Bilirubin (BR) nanoparticles.
The research team applied the properties of a bile pigment called BR, which exerts potent antioxidant and anti-inflammatory effects, to this research.
The team expects this research, which shows high biocompatibility as well as outstanding photoacoustic imaging and photothermal therapy, to be an appropriate system in the field of treatment for cancer.
In the past, the research team developed a PEGylated bilirubin-based nanoparticle system by combining water-insoluble BR with water-soluble Polyethylene Glycol (PEG).
This technology facilitated BR exerting antioxidants yet prevented them from being accumulated in the body. Its efficiency and safety was identified in an animal disease model, for conditions such as inflammatory bowel disease, islet cell transportation, and asthma.
Differing from previous research methods, this research applied the different physicochemical properties of BR to cancer treatment.
When the causative agent of jaundice, yellow BR, is exposed to a certain wavelength of blue light, the agent becomes a photonic nanomaterial as it responses to the light. This light-responsive nanomaterial can be used to cure jaundice because it allows for active excretion in infants.
Secondly, the team identified that BR is a major component of black pigment gallstones which can be often found in gall bladders or bile ducts under certain pathological conditions. The findings show that BR forms black pigment gallstones without the role of an intermediate or cation, such as calcium and copper. The research team combined cisplatin, a platinum metal-based anticancer drug, with BR so that BR nanoparticles changed the solution color from yellow to purple.
The team also examined the possibility of cisplatin-chelated BR nanoparticles as a probe for photoacoustic images. They found that considerable photoacoustic activity was shown when it was exposed to near infrared light. In fact, the photoacoustic signal was increased significantly in tumors of animals with colorectal cancer when the nanoparticles were administered to it intravenously. The team expects a more accurate diagnosis of tumors through this technology.
Moreover, the team assessed the photothermal effects of cisplatin-chelated BR nanoparticles. The research showed that the temperature of tumors increased by 25 degrees Celsius within five minutes when they were exposed to near infrared light, due to the photothermal effect. After two weeks, their size was reduced compared to that of other groups, and sometimes the tumors were even necrotized.
Professor Jon said, “Existing substances have a low biocompatibility and limitation for clinical therapy because they are artificially oriented; therefore, they might have toxicity. I am hoping that these cisplatin-chelated BR-based nanoparticles will provide a new platform for preclinical, translational research and clinical adaptation of the photoacoustic imaging and photothermal therapy.”
The paper (Dong Yun Lee as a first author) was published online in the renowned journal in the field of applied chemistry, Angewandte Chemi International Edition, on September 4. This research was sponsored by the National Research Foundation of Korea.
(Schematic diagram of the research)
(From left: Bilirubin nanoparticles, cisplatin-chelated Bilirubin nanoparticles)
2017.09.26 View 8121 -
Unlocking the Keys to Parkinson's Disease
A KAIST research team has identified a new mechanism that causes the hallmark symptoms of Parkinson’s disease, namely tremors, rigidity, and loss of voluntary movement.
The discovery, made in collaboration with Nanyang Technological University in Singapore, presents a new perspective to three decades of conventional wisdom in Parkinson’s disease research. It also opens up new avenues that can help alleviate the motor problems suffered by patients of the disease, which reportedly number more than 10 million worldwide. The research was published in Neuron on August 30.
The research team was led by Professor Daesoo Kim from the Department of Biological Sciences at KAIST and Professor George Augustine from the Lee Kong Chian School of Medicine at NTU. Dr. Jeongjin Kim, a former postdoctoral fellow at KAIST who now works at the Korea Institute of Science and Technology (KIST), is the lead author.
It is known that Parkinson’s disease is caused by a lack of dopamine, a chemical in the brain that transmits neural signals. However, it remains unknown how the disease causes the motor
Smooth, voluntary movements, such as reaching for a cup of coffee, are controlled by the basal ganglia, which issue instructions via neurons (nerve cells that process and transmit information in the brain) in the thalamus to the cortex. These instructions come in two types: one that triggers a response (excitatory signals) and the other that suppresses a response (inhibitory signals). Proper balance between the two controls movement.
A low level of dopamine causes the basal ganglia to severely inhibit target neurons in the thalamus, called an inhibition. Scientists have long assumed that this stronger inhibition causes the motor problems of Parkinson’s disease patients.
To test this assumption, the research team used optogenetic technology in an animal model to study the effects of this increased inhibition of the thalamus and ultimately movement. Optogenetics is the use of light to control the activity of specific types of neurons within the brain.
They found that when signals from the basal ganglia are more strongly activated by light, the target neurons in the thalamus paradoxically became hyperactive. Called rebound excitation, this hyperactivity produced abnormal muscular stiffness and tremor. Such motor problems are very similar to the symptoms of Parkinson’s disease patients. When this hyperactivity of thalamic neurons is suppressed by light, mice show normal movments without Parkinson’s disease symptoms. Reducing the levels of activity back to normal caused the motor symptoms to stop, proving that the hyperactivity caused the motor problems experienced by Parkinson’s disease patients.
Professor Kim at KAIST said, “This study overturns three decades of consensus on the provenance of Parkinsonian symptoms.” The lead author, Dr Jeongjin Kim said, “The therapeutic implications of this study for the treatment of Parkinsonian symptoms are profound. It may soon become possible to remedy movement disorders without using L-DOPA, a pre-cursor to dopamine.”
Professor Augustine at NTU added, “Our findings are a breakthrough, both for understanding how the brain normally controls the movement of our body and how this control goes awry during Parkinson’s disease and related dopamine-deficiency disorders.”
The study took five years to complete, and includes researchers from the Department of Bio & Brain Engineering at KAIST.
The research team will move forward by investigating how hyperactivity in neurons in the thalamus leads to abnormal movement, as well as developing therapeutic strategies for the disease by targeting this neural mechanism.
Figure abstract: Inhibitory inputs from the basal ganglia inhibit thalamic neurons (upper). In low-dopamine states, like PD, rebound firing follows inhibition and causes movement disorders (middle). The inhibition of rebound firing alleviates PD-like symptoms in a mouse model of PD.
2017.09.22 View 9516 -
Draining Eyes Clogged with Glaucoma
Professor Gou Young Koh in the Graduate School of Medical Science and Engineering and his team have identified a new mechanism involved in the development and progression of glaucoma, and found a potential therapeutic option to treat it. Glaucoma is the second cause of irreversible blindness, after cataracts. It affects about 3.5% of the world population aged 40 to 80.
Professor Koh also serves as the director of the Center for Vascular Research at the Institute for Basic Science. The IBS said the study, published in the Journal of Clinical Investigation, is expected to help the development of therapies to treat primary open-angle glaucoma (POAG), which counts for three quarters of all glaucoma patients.
One of the most important risk factors for glaucoma is the increased pressure inside the eye. A liquid called aqueous humor is constantly produced and drained out from the eye. It transports nutrients and inflates the eye giving it a roughly spherical shape. However, if this fluid cannot flow out of the eye chambers freely, an increase in intraocular pressure can damage the optic nerve, leading to vision loss. The precise mechanism of elevated resistance to aqueous humor outflow remains unclear, and although the current treatments for glaucoma tackle the production and outflow of aqueous humor, their outcomes are still poor.
A component of the eye that plays a fundamental role in draining out the aqueous humor is Schlemm's canal. It collects the aqueous humor and mediates its transfer from the eye chambers to blood circulation. The cells on the walls of the canal, endothelial cells, ship the liquid from the inner to the outer side in “packages”, called vacuoles. As the shape and number of the vacuoles reflects the outflow performance, several giant vacuoles are expected in the normal outflow process.
The team explained how imbalances in Schlemm's canal significantly increase the risk of glaucoma. They showed that an important regulator for canal functionality is the angiopoietin-Tie2 system. Angiopoietins, such as Ang1 and Ang2, are proteins important for the growth of new blood vessels and Tie2 is the receptor that binds them. It is known that the angiopoietin-Tie2 system plays a role in Schlemm’s canal formation, as Tie2 mutations or angiopoietin absence result in congenital glaucoma. However, this study clarified that it is also critically important during adulthood.
The researchers reported that adult mice deficient in Tie2 suffer from an elevated intraocular pressure, retinal neuronal damage and partial visual impairment. Moreover, they had a markedly decreased number of giant vacuoles inside Schlemm’s canal endothelial cells, which indicate a poor aqueous humor drainage.
The scientists also investigated if and how this process changes in older mice, as aging is a major risk factor for glaucoma, and showed that aged mice experience reduced levels of giant vacuoles, Tie2, Ang1, and Ang2, as well as other proteins connected with the angiopoietin-Tie2 pathway, like Prox1.
To test whether Tie2 activation could shift the situation, the researchers tested the antibody ABTAA (Ang2-binding and Tie2-activating antibody). They injected it in one eye of mice, while the other eye of the same mice functioned as the negative control. After one week, levels of Tie2 and Prox1, number and diameter of giant vacuoles in Schlemm’s canals increased in the ABTAA-treated eyes compared to control eyes. The researchers observed a similar outcome with decreased intraocular pressure when ABTAA was injected to the eyes of mice suffering from POAG with regressed Schlemm’s canals, indicating that this antibody might be considered as a therapeutic option.
"Slow development of glaucoma treatments is partly due to the poor understanding of the underlying pathogenesis," said Professor Koh, the corresponding author of the study. "We hope that identifying the critical role of the angiopoietin-Tie2 system in adult Schlemm’s canals will bring a significant boost in the development of therapeutics."
Figure 1: Schlemm's canal position inside the eye.
Schlemm's canal (green) plays a fundamental role in draining the aqueous humor (white arrows) from the anterior chamber of the eye to blood circulation. If the aqueous humor is not able to flow out freely, elevated intraocular pressure damages the optical nerve causing glaucoma and eventually blindness.
Figure 2: Electron microscope images reveal how the aqueous humor is packaged in vacuoles (arrowheads) inside the cells forming the walls of Schlemm's canal.
Aging and glaucoma cause the number and size of giant vacuoles to decrease, meaning that the aqueous humor outflow is compromised. The images compare the giant vacuoles in Schlemm's canals of a healthy mouse (top) and a mouse lacking Tie2 (bottom)
Figure 3: The Ang2-binding and Tie2-activating antibody (ABTAA) rejuvenates the eye of aged mice and rescues them from glaucoma.
Aging causes a reduction of the protein Tie2, a risk factor for increased intraocular pressure and glaucoma. In this experiment, one eye of mice lacking Ang1 and Ang2 was injected with the premixed ABTAA and Ang2, while the other eye was used as negative control. The researchers observed an increase in the area of Schlemm’s canal, together with higher levels of Tie2 (red) and lower intraocular pressure, suggesting that ABTAA restores the canal's functionality. The image includes the transcription factor Prox1 (green) and CD144 (blue), a protein present at the junctions between cells that form the wall of the canal. The angiopoietin-Tie2 system and Prox1 are linked by a vicious circle: the less Tie2 and Ang2, the less Prox1, leading to Schlemm's canal damage, increase in intraocular pressure, and acceleration of glaucoma progression.
2017.09.19 View 6696 -
Semiconductor Patterning of Seven Nanometers Technology Using a Camera Flash
A research team led by Professor Sang Ouk Kim in the Department of Materials Science and Engineering at KAIST has developed semiconductor manufacturing technology using a camera flash.
This technology can manufacture ultra-fine patterns over a large area by irradiating a single flash with a seven-nanometer patterning technique for semiconductors. It can facilitate the manufacturing of highly efficient, integrated semiconductor devices in the future.
Technology for the Artificial Intelligence (AI), the Internet of Things (IoTs), and big data, which are the major keys for the fourth Industrial Revolution, require high-capacity, high-performance semiconductor devices. It is necessary to develop lithography technology to produce such next-generation, highly integrated semiconductor devices.
Although related industries have been using conventional photolithography for small patterns, this technique has limitations for forming a pattern of sub-10 nm patterns.
Molecular assembly patterning technology using polymers has been in the spotlight as the next generation technology to replace photolithography because it is inexpensive to produce and can easily form sub-10 nm patterns. However, since it generally takes a long time for heat treatment at high-temperature or toxic solvent vapor treatment, mass production is difficult and thus its commercialization has been limited.
The research team introduced a camera flash that instantly emits strong light to solve the issues of polymer molecular assembly patterning. Using a flash can possibly achieve a semiconductor patterning of seven nanometers within 15 milliseconds (1 millisecond = 1/1,000 second), which can generate a temperature of several hundred degrees Celsius in several tens of milliseconds.
The team has demonstrated that applying this technology to polymer molecular assembly allows a single flash of light to form molecular assembly patterns.
The team also identified its compatibility with polymer flexible substrates, which are impossible to process at high temperatures. Through these findings, the technology can be applied to the fabrication of next-generation, flexible semiconductors.
The researchers said the camera flash photo-thermal process will be introduced into molecular assembly technology and this highly-efficiency technology can accelerate the realization of molecular assembly semiconductor technology.
Professor Kim, who led the research, said, “Despite its potential, molecular assembly semiconductor technology has remained a big challenge in improving process efficiency.” “This technology will be a breakthrough for the practical use of molecular assembly-based semiconductors.”
The paper was published in the international journal, Advanced Materials on August 21 with first authors, researcher Hyeong Min Jin and PhD candidate Dae Yong Park.
The research, sponsored by the Ministry of Science and ICT, was co-led Professor by Keon Jae Lee in the Department of Materials Science and Engineering at KAIST, and Professor Kwang Ho Kim in the School of Materials Science and Engineering at Pusan National University.
(1. Formation of semiconductor patterns using a camera flash)
(Schematic diagram of molecular assembly pattern using a camera flash)
(Self-assembled patterns)
2017.09.18 View 10150