Scientists Use the Tweaked Genes of a Virus to Halt Vision Loss

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iStock

What if you could tweak the genes of a virus to turn its ability to invade cells into a delivery system for eyesight therapy? That’s what researchers at Johns Hopkins School of Medicine say they’ve done by modifying an adenovirus, a type of virus that can infect tissue linings. The cutting edge gene therapy was developed to help those who suffer vision loss from a particular eye disorder—wet age-related macular degeneration (AMD).

Approximately 1.6 million Americans have AMD, the number one cause of vision loss. The disease is characterized by the growth of abnormal blood vessels that leak retinal fluid into the eye and destroy the macula, an area near the retina important for high acuity vision. This gene therapy both reduces fluid buildup and improves vision loss in humans, according to study results published in The Lancet.

The best current treatment for the disease requires injections of antibodies into the retina to suppress vascular endothelial growth factor (VEGF), a protein that is responsible for the growth of blood vessels—which in turn cause leaking fluid. But the problem is that patients must obtain these injections at four- to six-week intervals, or else the disease symptoms return and worsen over time. Peter Campochiaro, a professor of ophthalmology and neuroscience at Johns Hopkins Medicine's Wilmer Eye Institute and one of the authors of the study, explains that during this treatment, if a patient takes too long to get their next injection, the abnormal blood vessel net grows larger and recruits other cells. “That scarring causes permanent decrease in vision,” he tells Mental Floss. So over time, it’s common even for patients in treatment to “end up with less vision.”

His team has been working to make a form of injections that last longer, so patients don’t have to come in as frequently. For phase one of this trial, Campochiaro’s team recruited 19 participants to participate in a 52-week study. He was looking for people “who don’t have great visual potential, but have evidence of the disease process that you can measure in effect,” he says.

Since viruses are naturally good at getting into cells and depositing their genetic material, the researchers decided to modify a virus to deposit a gene that codes for a protein called sFLT01. sFLT01 blocks the factor that causes the abnormal vessels and fluid production. When the modified virus is injected into the eye, “the viral vector enters cells and deposits the gene, and the gene begins to produce the [sFLT01] protein,” he says. The protein binds to VEGF, preventing it from causing vessel growth and subsequent fluid leakage.

The 19 participants were divided into five different groups and given increasing doses of the viral vector. After determining there was no toxicity at the dose-limit of the first three groups, they proceeded to increase the dosage to its highest level.

Of the 11 participants with symptoms judged to be reversible, six showed “a substantial reduction in the fluid,” and four of those six saw “a pretty dramatic effect.” Those patients had big pockets of fluid in their retinas decrease, Campochiaro says. Better yet, the treatment lasted throughout the yearlong study, though the protein numbers peaked at 26 weeks, and then declined slightly (although not enough to reactivate disease symptoms).

In assessing why five patients saw no reduction in fluid, the scientists discovered those patients had pre-existing antibodies to the virus. They theorize that in these patients, the immune system may have killed the viral vector before it could deposit the genes, though they will have to do more research to prove this. This could be a problem in using this particular virus—a carrier virus called AAV2—since some 60 percent of patients tend to have these antibodies.

A possible solution might be to give resistant patients a surgical injection instead. During this procedure, scientists could take out the vitreous—a gel-like substance that gives your eye its round shape—and inject the vector surgically under the retina instead. While patients might prefer not to have surgery, “our data suggests that it doesn’t matter if there’s pre-existing antibodies [with this method],” he says.

Alternately, other viral vectors have proven to be more effective than AAV2, including a variation on the virus, AAV8, which provides better infections of the virus into the cell. Even more promising, the researchers recently finished a four-year study on a lentiviral vector (a totally different group of viruses) “that take [the genes] into the nucleus of the cell and inserts the gene right into the chromosomes,” Campochiaro explains.

His next steps will be to retest the treatment with a longer study period to identify just how long-lasting the effects are, as well as to test higher doses of the viral vector.

But right now, he is just excited that the gene therapy works. “We injected this gene, the gene is producing a protein, and you can measure that protein in the eye over time,” he says.

A Dracula Ant's Jaws Snap at 200 Mph—Making It the Fastest Animal Appendage on the Planet

Ant Lab, YouTube
Ant Lab, YouTube

As if Florida’s “skull-collecting” ants weren’t terrifying enough, we’re now going to be having nightmares about Dracula ants. A new study in the journal Royal Society Open Science reveals that a species of Dracula ant (Mystrium camillae), which is found in Australia and Southeast Asia, can snap its jaws shut at speeds of 90 meters per second—or the rough equivalent of 200 mph. This makes their jaws the fastest part of any animal on the planet, researchers said in a statement.

These findings come from a team of three researchers that includes Adrian Smith, who has also studied the gruesome ways that the skull-collecting ants (Formica archboldi) dismember trap-jaw ants, which were previously considered to be the fastest ants on record. But with jaw speeds of just over 100 miles per hour, they’re no match for this Dracula ant. (Fun fact: The Dracula ant subfamily is named after their habit of drinking the blood of their young through a process called "nondestructive cannibalism." Yikes.)

Senior author Andrew Suarez, of the University of Illinois, said the anatomy of this Dracula ant’s jaw is unusual. Instead of closing their jaws from an open position, which is what trap-jaw ants do, they use a spring-loading technique. The ants “press the tips of their mandibles together to build potential energy that is released when one mandible slides across the other, similar to a human finger snap,” researchers write.

They use this maneuver to smack other arthropods or push them away. Once they’re stunned, they can be dragged back to the Dracula ant’s nest, where the unlucky victims will be fed to Dracula ant larvae, Suarez said.

Researchers used X-ray imaging to observe the ants’ anatomy in three dimensions. High-speed cameras were also used to record their jaws snapping at remarkable speeds, which measure 5000 times faster than the blink of a human eye. Check out the ants in slow-motion in the video below.

14 Facts About Celiac Disease

iStock.com/fcafotodigital
iStock.com/fcafotodigital

Going gluten-free may be a modern diet trend, but people have been suffering from celiac disease—a chronic condition characterized by gluten intolerance—for centuries. Patients with celiac are ill-equipped to digest products made from certain grains containing gluten; wheat is the most common. In the short-term this can cause gastrointestinal distress, and in the long-term it can foster symptoms associated with early death.

Celiac diagnoses are more common than ever, which also means awareness of how to live with the condition is at an all-time high. Here are some things you might not know about celiac disease symptoms and treatments.

1. Celiac an autoimmune disease.

The bodies of people with celiac have a hostile reaction to gluten. When the protein moves through the digestive tract, the immune system responds by attacking the small intestine, causing inflammation that damages the lining of the organ. As this continues over time, the small intestine has trouble absorbing nutrients from other foods, which can lead to additional complications like anemia and osteoporosis.

2. You can get celiac disease from your parents.

Nearly all cases of celiac disease arise from certain variants of the genes HLA-DQA1 and HLA-DQB1. These genes help produce proteins in the body that allow the immune system to identify potentially dangerous foreign substances. Normally the immune system wouldn't label gliadin, a segment of the gluten protein, a threat, but due to mutations in these genes, the bodies of people with celiac treat gliadin as a hostile invader.

Because it's a genetic disorder, people with a first-degree relative (a sibling, parent, or child) with celiac have a 4 to 15 percent chance of having it themselves. And while almost all patients with celiac have these specific HLA-DQA1 and HLA-DQB1 variations, not everyone with the mutations will develop celiac. About 30 percent of the population has these gene variants, and only 3 percent of that group goes on to develop celiac disease.

3. Makeup might contribute to celiac disease symptoms.

People with celiac disease can’t properly process gluten, the protein naturally found in the grains like wheat, rye, and barley. Patients have to follow strict dietary guidelines and avoid most bread, pasta, and cereal, in order to manage their symptoms. But gluten isn’t limited to food products: It can also be found in some cosmetics. While makeup containing gluten causes no issues for many people with celiac, it can provoke rashes in others or lead to more problems if ingested. For those folks, gluten-free makeup is an option.

4. The name comes from 1st-century Greece.

A 1st-century Greek physician named Aretaeus of Cappadocia may have been the first person to describe celiac disease symptoms in writing [PDF]. He named it koiliakos after the Greek word koelia for abdomen, and he referred to people with the condition as coeliacs. In his description he wrote, “If the stomach be irretentive of the food and if it pass through undigested and crude, and nothing ascends into the body, we call such persons coeliacs.”

5. There are nearly 300 celiac disease symptoms.

Celiac disease may start in the gut, but it can be felt throughout the whole body. In children, the condition usually manifests as bloating, diarrhea, and abdominal discomfort, but as patients get older they start to experience more “non-classical” symptoms like anemia, arthritis, and fatigue. There are at least 281 symptoms associated with celiac disease, many of which overlap with other conditions and make celiac hard to diagnose. Other common symptoms of the disease include tooth discoloration, anxiety and depression, loss of fertility, and liver disorders. Celiac patients also have a greater chance of developing an additional autoimmune disorder, with the risk increasing the later in life the initial condition is diagnosed.

6. Some patients show no symptoms at all.

It’s not uncommon for celiac disease to be wrecking a patient’s digestive tract while showing no apparent symptoms. This form of the condition, sometimes called asymptomatic or “silent celiac disease,” likely contributes to part of the large number of people with celiac who are undiagnosed. People who are at high risk for the disease (the children of celiac sufferers, for example), or who have related conditions like type 1 diabetes and Down syndrome (both conditions that put patients at a greater risk for developing new autoimmune diseases) are encouraged to get tested for it even if they aren’t showing any signs.

7. It’s not the same as wheat sensitivity.

Celiac is often confused with wheat sensitivity, a separate condition that shares many symptoms with celiac, including gastrointestinal issues, depression, and fatigue. It’s often called gluten sensitivity or gluten intolerance, but because doctors still aren’t sure if gluten is the cause, many refer to it as non-celiac wheat sensitivity. There’s no test for it, but patients are often treated with the same gluten-free diet that’s prescribed to celiac patients.

8. It's not a wheat allergy either.

Celiac disease is often associated with wheat because it's one of the more common products containing gluten. While it's true that people with celiac can't eat wheat, the condition isn't a wheat allergy. Rather than reacting to the wheat, patients react to a specific protein that's found in the grain as well as others.

9. It can develop at any age.

Just because you don’t have celiac now doesn’t mean you’re in the clear for life: The disease can develop at any age, even in people who have tested negative for it previously. There are, however, two stages of life when symptoms are most likely to appear: early childhood (8 to 12 months) and middle adulthood (ages 40 to 60). People already genetically predisposed to celiac become more susceptible to it when the composition of their intestinal bacteria changes as they get older, either as a result of infection, surgery, antibiotics, or stress.

10. Not all grains are off-limits.

A gluten-free diet isn’t necessarily a grain-free diet. While it’s true that the popular grains wheat, barley, and rye contain gluten, there are plenty of grains and seeds that don’t and are safe for people with celiac to eat. These include quinoa, millet, amaranth, buckwheat, sorghum, and rice. Oats are also naturally gluten-free, but they're often contaminated with gluten during processing, so consumers with celiac should be cautious when buying them.

11. Celiac disease can be detected with a blood test.

Screenings for celiac disease used to be an involved process, with doctors monitoring patients’ reactions to their gluten-free diet over time. Today all it takes is a simple test to determine whether someone has celiac. People with the condition will have anti-tissue transglutaminase antibodies in their bloodstream. If a blood test confirms the presence of these proteins in a patient, doctors will then take a biopsy of their intestine to confirm the root cause.

12. The gluten-free diet doesn’t work for all patients.

Avoiding gluten is the most effective way to manage celiac disease, but the treatment doesn’t work 100 percent of the time. In up to a fifth of patients, the damaged intestinal lining does not recover even a year after switching to a gluten-free diet. Most cases of non-responsive celiac disease can be explained by people not following the diet closely enough, or by having other conditions like irritable bowel syndrome, lactose intolerance, or small intestine bacterial overgrowth that impede recovery. Just a small fraction of celiac disease sufferers don’t respond to a strict gluten-free diet and have no related conditions. These patients are usually prescribed steroids and immunosuppressants as alternative treatments.

13. If you don’t have celiac, gluten probably won’t hurt you.

The gluten-free diet trend has exploded in popularity in recent years, and most people who follow it have no medical reason to do so. Going gluten-free has been purported to do everything from help you lose weight to treat autism—but according to doctors, there’s no science behind these claims. Avoiding gluten may help some people feel better and more energetic because it forces them to cut heavily processed junk foods out of their diet. In such cases it’s the sugar and carbs that are making people feel sluggish—not the gluten protein. If you don’t have celiac or a gluten sensitivity, most experts recommend saving yourself the trouble by eating healthier in general rather than abstaining from gluten.

14. The numbers are growing.

A 2009 study found that four times as many people have celiac today than in the 1950s, and the spike can’t be explained by increased awareness alone. Researchers tested blood collected at the Warren Air Force Base between 1948 and 1954 and compared them to fresh samples from candidates living in one Minnesota county. The results supported the theory that celiac has become more prevalent in the last half-century. While experts aren’t exactly sure why the condition is more common today, it may have something to do with changes in how wheat is handled or the spread of gluten into medications and processed foods.

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