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Patients with a specific form of age-related macular degeneration (AMD), a leading cause of blindness in the United States, are also highly likely to have either underlying heart damage from heart failure and heart attacks, or advanced heart valve disease, or carotid artery disease associated with certain types of strokes, according to a new study from New York Eye and Ear Infirmary of Mount Sinai.
This research, published November 17 in BMJ Open Ophthalmology, is the first to identify which types of high-risk cardiovascular and carotid artery disease are linked to the eye disorder. The findings could prompt increased screening to save vision, diagnose undetected heart disease, and prevent adverse cardiovascular events.
“For the first time, we have been able to connect these specific high-risk cardiovascular diseases to a specific form of AMD, the one with subretinal drusenoid deposits (SDDs),” explains lead author R. Theodore Smith, MD, PhD, Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai. “This study is the first strong link between the leading cause of blindness, AMD, and heart disease, the leading cause of death worldwide. Furthermore, we also have strong evidence for what actually happens: the blood supply to the eye is directly diminished by these diseases, either by heart damage that diminishes blood supply throughout the body, or from a blocked carotid artery that directly impedes blood flow to the eye. A poor blood supply can cause damage to any part of the body, and with these specific diseases, the destroyed retina and leftover SDDs are that damage. Retinal damage means vision loss, and can lead to blindness.”
AMD is the leading cause of visual impairment and blindness in people over 65 and is the result of damage to the central area of the retina called the macula, which is responsible for reading and driving vision. One major form of early AMD consists of small yellow cholesterol deposits called drusen, which form under a part of the retina called the retinal pigment epithelium (RPE). They can deprive the retina of blood and oxygen, leading to vision loss. Drusen formation can be slowed by appropriate vitamin supplementation. The other major form of early AMD, subretinal drusenoid deposits (SDDs), are less well-known, and require high-tech retinal imaging to detect. These deposits contain a different form of cholesterol, and form above the RPE, and just beneath the light-sensitive retina cells, where the damage occurs and vision is lost. There is no known treatment for SDDs. Dr. Smith and a team of Mount Sinai researchers initially found that patients with cardiovascular disease or stroke were more likely to have SDDs. That first-of-its-kind research was published in the July issue of Retina. This new study expands on that previous work, looking at a larger patient population, and identifies the specific severe forms of heart disease and carotid artery disease that caused the SDDs of AMD.
Researchers analyzed the eyes of 200 AMD patients with retinal imaging to determine which patients had SDDs. Patients answered a questionnaire about their history of cardiovascular disease. Of the 200 patients, 97 had SDDs and 103 had drusen only. Forty-seven of the 200 had severe heart disease (19 had heart damage from heart failure or heart attack, 17 serious valve disease, and 11 stroke stemming from the carotid artery). Forty of the 47 (86 percent) had SDDs. By contrast, of the 153 AMD patients who did not have these severe diseases, 57 had SDDs (43 percent). The researchers concluded that AMD patients with these severe cardiovascular diseases and stroke were nine times more likely to have SDDs than those without them.
“This work demonstrates the fact that ophthalmologists may be the first physicians to detect systemic disease, especially in asymptomatic patients,” says co-investigator Richard B. Rosen, MD, Chief of the Retina Service for the Mount Sinai Health System. “Detecting SDDs in the retina should trigger a referral to the individual’s primary care provider, especially if no previous cardiologist has been involved. It could prevent a life-threatening cardiac event.”
“This study has opened the door to further productive multidisciplinary collaboration between the Ophthalmology, Cardiology and Neurology services,” says Jagat Narula, MD, PhD, Director of the Cardiovascular Imaging Program at the Zena and Michael A. Wiener Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai. “We should also focus on defining the disease severity by vascular imaging in cardiology and neurology clinics, and assess their impact on AMD and SDDs with retinal imaging. In this way we can learn which vascular patients should be referred for detection and prevention of blinding disease.”
This study was funded by a Regeneron Pharmaceuticals Investigator-Initiated Study, Research to Prevent Blindness Challenge Grant, the Macula Foundation, a Bayer-Global Ophthalmology Award, and the International Council of Ophthalmology-Alcon Fellowship.

Immunotherapy is a cutting-edge approach to treating cancer by turning the patient’s own immune system against their tumor. Our increasing knowledge of the mechanisms by which the body regulates immune responses has been transformative to our fight against cancer.
But despite success rates, immunotherapy has time and again met with a stubborn obstacle: tumor cells often evade the “radar” of immune cells seeking to destroy them. This in turn leads to treatment resistance, which in many cases would benefit from a deeper understanding of mechanisms that can help circumvent it.
A new study led by scientists at EPFL has now uncovered a protein that plays a key role in helping tumors evade immune destruction. The protein, named “fragile X mental retardation protein” (FMRP), regulates a network of genes and cells in the tumor microenvironment that contribute to its ability to “hide” from immune cells. Normally, FMRP is involved in regulating protein translation and the stability of mRNA in neurons. But the researchers found that it is aberrantly up-regulated in multiple forms of cancer.
The study, published in Science, was led by researchers in the group of Douglas Hanahan at the Swiss Institute for Experimental Cancer Research (ISREC) and the Lausanne Branch of the Ludwig Institute for Cancer Research, along with colleagues from the University Hospital of Lausanne (CHUV) and other Swiss institutions. The discovery has also led to an EPFL spin-off, Opna Bio, whose staff were also involved in the research.
But why FMRP? The idea came from previous studies showing that cancer cells that naturally overexpress FMRP are invasive and metastatic. Other studies show that if, in contrast, FMRP fails to be expressed in developing neurons it can lead to cognitive defects (hence the “mental retardation” part of the protein’s name).
With this evidence in mind, the researchers set off to investigate the expression of FMRP in human tumors. They then assessed its tumor-promoting functions in mouse models of cancer, and finally studied its association with prognosis for human cancer patients.

A promising new study released by the University of Colorado Cancer Center suggests that recurrence of certain cancers can be significantly decreased by irradiating only a select set of lymph nodes near a tumor rather than all of them.
The study was published today in Nature Communications.
“Doctors have traditionally irradiated all the lymph nodes surrounding a tumor in a process called ‘elective nodal irradiation,'” said Sana Karam, MD, PhD, associate professor of radiation oncology at the University of Colorado School of Medicine and the study’s senior author. “But the problem with this scorched-earth approach in the era of immunotherapy is that doing so also eliminates the source of imune cells for the immunotherapy to work on. Lymph nodes are the hub for priming and expanding the major immune cells that can go and fight the cancer.”
Karam and her team learned that irradiating all of the lymph nodes around a tumor significantly decreased immune memory and antigen spread, creating a much greater risk of the cancer spread in parts of the body far away from the tumor’s original site. “That was an unexpected finding,” says Karam.
The team tested this theory pre-clinicaly on several different tumor models of head and neck, along with a breast cancer and melanoma model. The result was the same regardless of the type of cancer being treated. When radiation killed the immune cells that could recognize what the cancer looked like, the patient’s immune system lost the ability to fight the cancer systemically.
On the other hand, the researchers found that irradiating certain lymph nodes known as sentinel lymph nodes was absolutely critical. Failure to irradiate those resulted in recurrence nearby.
“This study confirms why elective nodal irradiation has long been the clinical standard of care, as it does decrease regional recurrence,” said Laurel B. Darragh, the paper’s first author and an MD/PhD student in Dr. Karam’s lab. “But it also shows that to combine radiation with immunotherapy effectively, we need to reevaluate our strategies and restrict nodal irradiation to the sentinel lymph nodes. This eliminates regional neck recurrence, and far away spread, while preserving long-term, systemic immune response.”
The findings were corroborated by data from a recent human patient clinical trial where pre-surgical radiation was limited to the gross tumor and the sentinel lymph nodes while avoiding all other lymph nodes so as to sustain immune memory. Researchers found that the immune system in these patients was highly activated, which has been shown to correlate with a better prognosis.
“We’re hopeful that this data will set the stage for future clinical trial design, not only reducing patients’ side effects but also improving long-term outcomes,” said Karam.
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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Laura Kelley. Note: Content may be edited for style and length.

Race- and ethnicity-based discrepancies in exposure to air pollution, especially regarding proximity to roadways and industrial zones, are well-established. A new study reports the first nationwide patterns in atmospheric fine particulate pollution and nitrogen dioxide exposure at U.S. public schools.
On both national and local scales, schools with more students of color and students who receive free or reduced-price lunches, a proxy for poverty, are located in areas with higher concentrations of the pollutants, the study found. The study, led by members of NASA’s Health and Air Quality Applied Science team, was published in GeoHealth, AGU’s journal for research that investigates the intersection of human and planetary health for a sustainable future.
The study analyzed the distribution of two pollutants, particulate matter of 2.5 microns in diameter and smaller (PM2.5) and nitrogen dioxide, and compared pollutants to students’ racial or ethnic identity and income status. PM2.5 can cause short-term irritation and exacerbate chronic conditions such as asthma and heart disease. Nitrogen dioxide can also cause irritation and either bring about or worsen respiratory conditions. Long-term exposure to both pollutants can result in increased risk of hospitalization or death.
“School kids are a really vulnerable population,” said Michael Cheeseman, an atmospheric scientist at Colorado State University and lead author of the new study. “They’re really sensitive to air pollution, and they spend a lot of their time at school.”
In the U.S., children spend an average of nearly 7 hours per day at school for 180 days of the year. School-aged children are also still developing, and studies have found exposure to air pollution may hurt children’s health, including their brain development, lung health, and ability to learn, Cheeseman said.
The study used existing datasets* of student populations across the continental U.S. and satellite-derived concentrations of the pollutants from 2017 through 2019, with pollutant estimations verified by established EPA monitoring networks. One of the pollutant models explicitly accounts for nitrogen dioxide derived from traffic, which is especially relevant for low-income schools because they tend to be located near busy roadways. The pollutants reflect ambient air pollution, not air pollution inside school buildings.

A new Johns Hopkins study shows that data gathered from wearable activity trackers can be used to obtain several metrics associated with the user’s general physical health and cardiovascular health status. While these sensors are generally marketed as daily step counters, the Johns Hopkins research team believes they could potentially serve a greater purpose: supporting clinical care for patients with pulmonary arterial hypertension (PAH) and other chronic diseases.
The study was published in npj Digital Medicine on Nov. 9.
“The purpose of this study was to show that clinically relevant metrics beyond daily step count can be derived from these wearable activity monitors,” says Zheng “Peter” Xu, Ph.D., the study’s first author and a postdoctoral fellow for inHealth, a strategic initiative to advance precision medicine at The Johns Hopkins University. “Historically, remote monitoring of a patient’s physical status has been challenging. We wanted to meet that challenge and see what kind of untapped information is contained within these devices that could help us support patients with PAH.”
The Cleveland Clinic provided the Johns Hopkins research team with activity tracker-obtained data for 22 individuals with PAH who wore activity trackers between two clinic visits. At both clinic visits, Cleveland Clinic medical professionals recorded 26 health measurements of each participant, including health-related quality of life, heart rate measurements and results from the commonly used aerobic capacity and endurance test known as the six-minute walk distance (6MWD) test.
Using the minute-to-minute step rate and heart rate data of each participant, the Johns Hopkins team ascertained several metrics broadly associated with physical health and cardiovascular function. These included the distribution of heart rate and intensity and frequency of walking instances throughout each week, as well as results from an analog version of the 6MWD test that the team dubbed the free-living six-minute walk distance test. These data enabled the team to understand each participant’s health status and to identify subgroups among participants with similar metrics to one another.
To demonstrate that these data have potential for clinical use, the team also compared the activity-tracker metrics with the 26 health metrics recorded during both clinic visits — and found some unexpected correlations. For example, an activity tracker-measured fitness assessment (based on step count and heart rate data) correlated with levels of clinically measured NT-proBNP, a blood biomarker used to assess risk of heart failure. Across the 22 participants, the research team found statistically significant differences in 18 of these metrics.
“Finding so many statistically significant differences in a relatively small cohort suggests to us that activity-tracker data may make it possible to identify surrogate markers of disease severity that can be monitored remotely,” says Peter Searson, Ph.D., senior author of the study and the Joseph R. and Lynn C. Reynolds Professor at the Johns Hopkins University Whiting School of Engineering. “These data could potentially contribute to the identification of patients who would benefit from more frequent clinic visits or specific medications.”
“We also believe that activity tracker-measured health parameters could serve as proxies for clinically measured health parameters of patients with chronic disease,” adds Searson.
Next, the research team is exploring whether these devices could support clinical care for patients with chronic obstructive pulmonary disease (COPD) and scleroderma. Collaborating with the Johns Hopkins COPD Precision Medicine Center of Excellence, they will seek to determine whether signals derived from activity trackers can be used to predict the risk of a COPD flareup.
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Researchers led by Hidetoshi Masumoto and Genshiro Sunagawa at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have developed a new method of protecting organs during heart and aortic surgery when blood circulation has to be blocked. Rather than relying on cold temperatures to induce hypometabolism and reduce the need for oxygen, the technique works by stimulating Q neurons in the brain, which slow metabolism down to a hibernation-like state. In this proof-of-concept study, the procedure protected mouse kidneys from damage due to lack of oxygen and avoided harmful side effects related to extended hypothermia. The findings could lead to new ways of performing similar surgeries in people.
For some kinds of heart and aortic surgery, doctors must cut off blood circulation as they work to repair the aorta. For the last 50 years, this type of surgery has been performed after using cold temperatures to induce deep hypothermia, which slows down the body’s metabolism so that organs can survive with very little oxygen. While this is effective in protecting organs like the kidneys, it also reduces blood coagulation, causing excessive bleeding and the need for blood transfusions.
Masumoto and his team at RIKEN BDR have been looking for ways to slow down metabolism without inducing hypothermia. We know that many animals — such as bears and squirrels — can hibernate, and that despite the extremely slow metabolism during hibernation, they are healthy when they wake up. However, like most animals, people do not hibernate. This was the end of the story until a few years ago when Sunagawa’s group discovered a way to induce a hibernation-like state in mice — animals that do not normally hibernate. “If we can induce them, there are many possibilities for using hibernation-like states in cardiovascular medicine, resuscitation medicine, or other cases in which organ protection via hypothermia is insufficient or inappropriate,” says Sunagawa.
But first, the technique’s effectiveness needs to be verified in animal models. The new study is the first clinical implementation of the technique, and tested its effectiveness using a mouse model of aortic surgery that requires circulatory arrest. The team’s previous studies showed that hibernation-level hypometabolism could be achieved by activating special neurons in the brain’s hypothalamus called Q neurons. Chemogenetic biotechnology allowed the researchers to trigger activation of these specific neurons with an injection. They compared four groups of model mice that varied in whether or not cold temperatures were used to induce hypometabolism and whether or not Q neurons were activated.
Kidney damage and renal function were evaluated by looking at levels of biomarkers in the blood. Analysis showed hypometabolism induced by Q-neurons at normal temperatures protected the kidneys as well as that induced using hypothermia. “With these results, we now know that Q neurons induced hibernation-like states can be used to protect organs,” says Masumoto.
The ultimate goal of Masumoto and Sunagawa’s research is to slow down people’s metabolism during heart surgery, or for other medical reasons, using some variation of this technique. But because Q neurons in people cannot be selectively activated the way they can in experimentally engineered mice, the team is now looking at ways to protect organs downstream from the brain. “Activating Q neurons triggers some sequence of biological events that allows organs to exist in a hypometabolic state for days,” explains Sunagawa. “Once we know precisely what these events are, we are confident we can induce them pharmacologically in the body, without needing to first activate the Q neurons.”
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Researchers from Indiana University School of Medicine have identified a protein that interacts and enhances the spread of neurotoxic species of tau — which is primarily found in neurons that appear abnormal in the brains of Alzheimer’s disease patients.
The study, recently published in Nature Neuroscience, was led by Cristian Lasagna-Reeves, PhD, associate professor of anatomy, cell biology, and physiology, and Pablo Martinez, PhD, postdoctoral fellow in anatomy, cell biology, and physiology and first author of the paper.
The research team found that bassoon, a presynaptic scaffolding protein, contributes to tau-seed propagation and neurotoxicity. They investigated the role of bassoon on tau through mouse and drosophila (fruit flies) models as well as human cell and human brain samples.
“The major novelty of this study is that we were the first ones to find the interactome of the tau seed, which is a tau species that represents less than 5% of total tau in the brain,” Lasagna-Reeves said. “We’re trying to determine the proteins that are only interacting with the tau seed.”
The tau seed is the species of tau that propagates in the brain, moving from one neuron to the next producing neurodegeneration, Lasagna-Reeves said. In Alzheimer’s disease patients, the protein tau, which normally helps stabilize microtubules, is misfolded and abnormally shaped.
Previous studies into tau’s effect on neurodegeneration have identified proteins that interact with the majority of tau in the brain. Lasagna-Reeves said said by narrowing their study to the tau seed and the proteins it interacts with — which results in neurotoxic events in the brain — it could lead to a more targeted approach in therapeutics against Alzheimer’s disease.
The researchers discovered that bassoon exacerbates tau seeding and toxicity in both mouse and drosophila models. Bassoon stabilizes the tau seed, which allows it to propagate in the brain. The protein acts as a scaffold, Lasagna-Reeves said; if bassoon is removed, it will make the tau seed more unstable. Martinez said by lowering the level of bassoon in the models, it decreased the spread of tau, reduced brain atrophy and improved synaptic and behavior impairments of the disease.
“We proved that there is a small portion of tau in the brain that is very toxic in Alzheimer’s disease and other neurodegenerative diseases, and we determined how important these interactors are to the tau seed,” Martinez said. “The main message for the future is to target bassoon as well as other proteins that interact with the tau seed and translate that to therapies.”
The lab is collaborating with the IU School of Medicine-Purdue TaRget Enablement to Accelerate Therapy Development for Alzheimer’s Disease (TREAT-AD) drug discovery center to target bassoon through potential therapeutics that downregulate the protein in the brain.
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Colorectal carcinoma is the second most common cause of cancer death in Germany. Although cancer research in recent years has been able to significantly improve early diagnosis and therapy, the resistance of advanced colorectal tumours to common chemotherapies still constitutes a major problem and contributes substantially to the high mortality rate of patients with such tumours.
When chemotherapeutic agents cause colon cancer cells to die, they release ATP (adenosine triphosphate) molecules, the cell’s energy currency, as a messenger substance. Researchers led by Professor Florian Greten at Georg-Speyer-Haus have now corroborated this in experiments. This ATP binds to certain receptors (P2X4 purinoreceptors) on the surface of surrounding tumour cells. This activates an important survival signalling pathway in these neighbouring cells, which protects them from cell death and makes the tumour resistant to therapy.
The cells killed off by the chemotherapy “warn” their neighbouring cells, as it were, and at the same time provide them with a survival strategy. However, if the communication between the dying tumour cells and their neighbours is interrupted — as the scientists were able to show in preclinical models — this raises the efficiency of the chemotherapy many times over, and tumours that were initially resistant respond very well to it.
Dr Mark Schmitt, first author of the study, explains: “Our research results demonstrate that — despite years of successful research — unknown mechanisms are still being discovered which show us how perfidiously tumour cells evade therapy. Our results now offer a new and promising starting point for substantially improving the response rate of advanced colorectal carcinomas to common chemotherapeutic agents by means of combination therapy.”
Professor Florian Greten, director of Georg-Speyer-Haus and spokesperson for the LOEWE Centre Frankfurt Cancer Institute explains: “We were surprised to see that tumour cells have developed communication mechanisms to the point that even the dying ones play an active role in ensuring their neighbours’ survival when under therapeutic ‘attack’. We hope very much that by interrupting the communication between the cells we can achieve this tremendous increase in the effect of standard therapy in patients as well.” The team now wants to work with colleagues at the Frankfurt Cancer Institute to test this new therapeutic concept in patients.
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Encapsulating cells — both prokaryotic and eukaryotic — allows researchers to carry out experiments in hydrated environments over prolonged periods of time. However, cell growth under these conditions can exert a lot of pressure on the encapsulating shells, resulting in cell leakage. In a new study, researchers at the University of Illinois Urbana-Champaign have developed modified alginate hydrogels that can endure the growth of bacteria, allowing them to synthesize important enzymes.
Hydrogels are polymers that are reinforced by different chemical bonds, and are capable of absorbing water and swelling without breaking down. As a result, biotechnology researchers have often turned to these structures to provide stability and structural support for their cell cultures.
“Hydrogel capsules have been utilized for over 50 years. There are many different types that can be made by combining different kinds of cells in different hydrogel environments,” said Yoon Jeong, a graduate student in the Irudayaraj (CGD/EIRH) lab. “The problem with combining microorganisms with hydrogel capsules is that they leak out.”
To address this problem, Jeong decided to focus on alginate, a naturally occurring, edible compound found in brown algae. Although it has been previously looked at, using it to encapsulate bacteria has been challenging.
“My strategy was to make a hydrogel membrane on the surface of the hydrogel structure,” Jeong said. Although the change may seem small, it works well. Jeong tested his system with genetically-modified Lactococcus lactis and saw that without the layer, the bacteria leaked out and were unable to form biofilms — a collection of microorganisms that stick to each other. On the other hand, L. lactis colonies inside the modified hydrogels were able to grow for over 10 days; the hydrogels provided a stable platform that did not rupture.
Jeong also looked genetically-modified Escherichia coli, which can synthesize a host of different molecules, only when they are able to achieve a high cell density. He looked at E. coli cells that can produce green fluorescent protein, which emits a green signal when the cells are subjected to ultraviolet light. “Although growing GFP-producing E. coli is simple, they quickly die,” Jeong said. “I showed that inside the hydrogel they form colonies, which continuously increase in size, produce GFP, and do not leak out.”
He achieved the same results when he used E. coli cells that are bioluminescent. These bacteria encode the lux genes that result in blue cells that glow in the dark. The researchers saw that once the bacteria reached a certain cell density, the luminescence continued to increase for the next 3 days.
The main purpose of making these hydrogels is to develop bioreactors that can support the growth of bacteria while they make important compounds. To test whether the modified hydrogels were capable of sustaining such processes, Jeong also tested the ability of L. lactis to make nisin, a peptide that is used as a food preservative. In agreement with their previous results, the bacteria were able to grow well in the modified hydrogels and were able to produce the compound.
“Although at a glance it can seem simple to make these hydrogel structures, it is actually difficult. You have to control their size, thickness, and prevent agglomeration since these capsules stick together,” Jeong said. “Researchers who have a different scientific background have found this process difficult. We plan to publish a detailed protocol soon so that people can use this cheap and easy technique.”
The researchers are also interested in continuing their tests in human and cancer cells, with the hope that the hydrogels will be able to provide a reliable platform for a wide range of applications.
The work was partially funded by the National Institute of Biomedical Imaging and Bioengineering of the NIH.

You can keep your best guesses. Engineers at Rice University’s George R. Brown School of Engineering are starting to understand exactly what goes on when doctors pump contrast agents into your body for an MRI scan.
In a new study that could lead to better scans, a Rice-led team digs deeper via molecular simulations that, unlike earlier models, make absolutely no assumptions about the basic mechanisms at play when gadolinium agents are used to highlight soft tissues.
The study led by Rice chemical and biomolecular engineer Philip Singer, former associate research professor Dilip Asthagiri, now of Oak Ridge National Laboratory, and graduate student Thiago Pinheiro dos Santos appears in Physical Chemistry Chemical Physics.
It employs the sophisticated models first developed at Rice for oil and gas studies to conclusively analyze how hydrogen nuclei at body temperatures “relax” under nuclear magnetic resonance (NMR), the technology used by magnetic resonance imaging, aka MRI.
Doctors use MRI to “see” the state of soft tissues, including the brain, in a patient by inducing magnetic moments in the hydrogen nuclei of water molecules to align with the magnetic field, a process that can be manipulated when gadolinium agents are in the vicinity. The device detects bright spots when the aligned nuclei relax back to thermal equilibrium following an excitation. The faster they relax, the brighter the contrast.
Gadolinium molecules are naturally paramagnetic and sensitive to magnetic excitation. Because they’re toxic, they are usually chelated when part of a contrast agent. “A chelate basically hugs the gadolinium and protects your body from directly interacting with the metal,” Pinheiro dos Santos said. “We’re asking, exactly how do these molecules behave?”
Though gadolinium-based contrast agents are injected by the ton into patients each year, how they work on a molecular level has never been fully understood.