Biomarkers could aid in early detection of glaucoma

Researchers bred mice in which the gene PTP-Meg2 (protein tyrosine phosphatase megakaryocyte 2) was mutated. As a result, the animals suffered from chronic intraocular pressure elevation. The research team successfully demonstrated that, in their model, the intraocular pressure elevation was associated with a loss of optic nerve fibers and retinal cells. They also observed that retinal cells were unable to function properly. They further discovered glial cells and certain components of the immune system showed a reaction in the animals’ optic nerve and retina. As both aspects may be relevant for neurodegeneration, specific and early intervention into these cellular mechanisms could inhibit glaucoma.

By making use of a genetic screening, the researchers identified new potential biomarkers for glaucoma, which in the future, may facilitate early detection. As a result, it will be possible to start therapy at an earlier stage, before the optic nerve and retina are damaged. The glaucoma-mouse model may, moreover, be used to test new therapy options. So far intraocular pressure was reduced and nerve cells were retained in the mice if they were given a drug that has been used to treat human patients.

With more than 60 million patients, Glaucoma is a leading cause of blindness worldwide. In Germany alone, there are one million patients — and the estimated number of unknown cases is likely to be much higher, due to the fact that symptoms often remain undetected during the early stage of the disease. In glaucoma patients, the optic nerve and the retinal nerve cells are damaged beyond repair.

To read the original article in its entirety, click here. https://www.sciencedaily.com/releases/2018/10/181025103308.htm

AMAZING: Congenital blindness reversed in mice!

Researchers funded by the National Eye Institute (NEI) have reversed congenital blindness in mice by changing supportive cells in the retina called Müller glia into rod photoreceptors. The findings advance efforts toward regenerative therapies for blinding diseases such as age-related macular degeneration and retinitis pigmentosa.

“This is the first report of scientists reprogramming Müller glia to become functional rod photoreceptors in the mammalian retina,” said Thomas N. Greenwell, Ph.D., NEI program director for retinal neuroscience. “Rods allow us to see in low light, but they may also help preserve cone photoreceptors, which are important for color vision and high visual acuity. Cones tend to die in later-stage eye diseases. If rods can be regenerated from inside the eye, this might be a strategy for treating diseases of the eye that affect photoreceptors.”

Photoreceptors are light-sensitive cells in the retina, located in the back of the eye, that signal the brain when activated. In mammals, including mice and humans, photoreceptors fail to regenerate on their own. Like most neurons, once mature they no longer divide.

Scientists have long studied the regenerative potential of Müller glia because in other species, such as zebrafish, they divide in response to injury and can turn into photoreceptors and other retinal neurons. The zebrafish can thus regain vision after severe retinal injury. In the lab, however, scientists can coax mammalian Müller glia to behave more like they do in the fish. But it requires injuring the tissue.

“From a practical standpoint, if you’re trying to regenerate the retina to restore a person’s vision, it is counterproductive to injure it first to activate the Müller glia,” said Bo Chen, Ph.D. “We wanted to see if we could program Müller glia to become rod photoreceptors in a living mouse without having to injure its retina,” said Chen, the study’s lead investigator.

In phase one of a two-phase reprogramming process Chen’s team spurred Müller glia in normal mice to divide by injecting their eyes with a gene to turn on a protein called beta-catenin. A few weeks later, in phase two, they injected the mice’s eyes with factors that encouraged the newly divided cells to develop into rod photoreceptors.

The researchers found that the newly formed rod photoreceptors looked structurally no different from real photoreceptors.  Additionally, synaptic structures that allow the rods to communicate with other types of neurons within the retina had also formed. To determine whether the Müller glia-derived rod photoreceptors were functional, they tested the treatment in mice with congenital blindness, which meant that they were born without functional rod photoreceptors.

In the treated mice that were born blind, Müller glia-derived rods developed just as effectively as they had in normal mice. Functionally, they confirmed that the newly formed rods were communicating with other types of retinal neurons across synapses. Furthermore, light responses recorded from retinal ganglion cells — neurons that carry signals from photoreceptors to the brain — and measurements of brain activity confirmed that the newly-formed rods were in fact integrating in the visual pathway circuitry, from the retina to the primary visual cortex in the brain.

Chen’s lab is conducting behavioral studies to determine whether the mice have gained the ability to perform visual tasks such as a water maze task. Chen also plans to see if the technique works on cultured human retinal tissue.

This is a fascinating development and one that we will definitely be following.

To read the original article in its entirety, click here. https://www.sciencedaily.com/releases/2018/08/180815130544.htm

Eye exams may one day predict Alzheimer’s

One day in the not too distant future, it may be possible to screen patients for Alzheimer’s disease using an eye exam.

By using technology similar to what is already found in many eye doctors’ offices, researchers at Washington University School of Medicine in St. Louis have detected evidence suggesting Alzheimer’s in older patients who had no symptoms of the disease.

“This technique has great potential to become a screening tool that helps decide who should undergo more expensive and invasive testing for Alzheimer’s disease prior to the appearance of clinical symptoms,” said the study’s first author, Bliss E. O’Bryhim, MD, PhD,. “Our hope is to use this technique to understand who is accumulating abnormal proteins in the brain that may lead them to develop Alzheimer’s.”

Substantial brain damage from Alzheimer’s disease can occur years before any symptoms such as memory loss and cognitive decline appear. Scientists estimate that Alzheimer’s-related plaques can build up in the brain two decades before the onset of symptoms, so researchers have been looking for ways to detect the disease sooner.

Physicians now use PET scans and lumbar punctures to help diagnose Alzheimer’s, but they are both expensive and invasive.

Previous studies that involved examining the eyes of people who had died from Alzheimer’s had reported that the eyes of such patients showed signs of thinning in the center of the retina and degradation of the optic nerve.

In the new study, the researchers used a noninvasive technique — called optical coherence tomography angiography — to examine the retinas in eyes of 30 study participants with an average age in the mid 70s, none of whom exhibited clinical symptoms of Alzheimer’s.

Those participants were patients in The Memory and Aging Project at Washington University’s Knight Alzheimer’s Disease Research Center

“In the patients with elevated levels of amyloid or tau, we detected significant thinning in the center of the retina,” said one of the researchers “All of us have a small area devoid of blood vessels in the center of our retinas that is responsible for our most precise vision. We found that this zone lacking blood vessels was significantly enlarged in people with preclinical Alzheimer’s disease.”

The eye test used in the study shines light into the eye, allowing a doctor to measure retinal thickness, as well as the thickness of fibers in the optic nerve. A form of that test often is currently available in some optometrist and most ophthalmologist’s offices. In fact, the Mettawa office of Visibly Better Eye Care has the OCT machine needed to perform this test, but as of yet they are not offering this service.

For purpose of this study, however, the researchers added a new component to the more common test: angiography, which allows doctors to distinguish red blood cells from other tissue in the retina.

“The angiography component allows us to look at blood-flow patterns,” said the other co-principal investigator said. “In the patients whose PET scans and cerebrospinal fluid showed preclinical Alzheimer’s, the area at the center of the retina without blood vessels was significantly larger, suggesting less blood flow.”

“The retina and central nervous system are so interconnected that changes in the brain could be reflected in cells in the retina.”

Of the patients studied, 17 had abnormal PET scans and/or lumbar punctures, and all of them also had retinal thinning and significant areas without blood vessels in the centers of their retinas. The retinas appeared normal in the patients whose PET scans and lumbar punctures were within the typical range.

“We know the pathology of Alzheimer’s disease starts to develop years before symptoms appear, but if we could use this eye test to notice when the pathology is beginning, it may be possible one day to start treatments sooner to delay further damage,” one of the researchers said.

To read the original article in its entirety, click here. https://www.sciencedaily.com/releases/2018/08/180823140921.htm

Human retinas grown in a dish show how color vision develops

Human retinas were grown from scratch by biologists at Johns Hopkins University to determine how cells that allow people to see color develop.

The research lays the foundation for researchers to develop therapies for eye diseases such as color blindness and macular degeneration.

“Everything we examine looks like a normal developing eye, just growing in a dish,” said Robert Johnston, a developmental biologist at Johns Hopkins. “You have a model system that you can manipulate without studying humans directly.”

Johnston’s lab explores what happens in the womb to turn a developing cell into a specific type of cell, an aspect of human biology that is largely unknown.

Johnston and his team focused on the cells that allow people to see blue, red and green — the three cone photoreceptors in the human eye.

Previously the majority of vision research has been on mice and fish, neither of these species has the dynamic daytime and color vision of humans. So Johnston’s team had to create the human eyes they needed — with stem cells.

“Trichromatic color vision delineates us from most other mammals,” said lead author Kiara Eldred, a Johns Hopkins graduate student. “Our research is really trying to figure out what pathways these cells take to give us that special color vision.”

Over several months, as the cells grew in the lab and became full-blown retinas, the team found the blue-detecting cells materialized first, followed by the red- and green-detecting ones. They found the key to the molecular switch was the ebb and flow of thyroid hormone. Important to note is the level of this hormone wasn’t controlled by the thyroid gland, which of course isn’t in the dish, but entirely by the eye itself.

“What’s exciting about this is our work establishes human organoids as a model system to study mechanisms of human development,” Johnston said. “What’s really pushing the limit here is that these organoids take nine months to develop just like a human baby. So what we’re really studying is fetal development.”

This groundbreaking work can lead to all sorts of applications is the vision deficiency arena.

To read the article in its entirety click here.  https://www.sciencedaily.com/releases/2018/10/181011143112.htm

A common Diabetes medication may actually help prevent development of Macular Degeneration, a common cause of blindness

According to an article published on October 29, 2018 by American Academy of Ophthalmology Researchers from Taiwan have shown that people with type-2 diabetes who were treated with Metformin showed a significantly lower rate of age-related macular degeneration (AMD).The study further suggests that the anti-inflammatory and anti-oxidative effects of metformin can protect against AMD while also controlling diabetes. The research was presented at AAO 2018, the 122nd Annual Meeting of the American Academy of Ophthalmology.

It has been long known that inflammation and oxidative stress play a key role in the development of both diabetes and AMD. Since metformin suppresses inflammation and oxidative stress, researchers in Taiwan theorized that it was possible that the diabetes drug could also protect against AMD, one of the leading causes of blindness in Americans over age 50, currently affecting about 2.1 million people in the United States alone.

The researchers used the Taiwan National Health Insurance Research Database, to collect data on all patients recently diagnosed with type 2 diabetes from January 2001 to December 2013, dividing them into two groups: Those who took metformin (45,524 patients) and those who did not (22,681 patients). After following both groups for 13 years, the researchers found that patients in the metformin group had a significantly lower risk of developing AMD. In fact, half as many patients in the metformin group had AMD compared to the control group.

“Our study is the first to reveal the protective effect of metformin on the development of AMD,” said lead investigator, Yu-Yen Chen, M.D. “While more study is required to determine just how metformin protects against the development of AMD, this is an exciting development for patients at risk.”

AMD is a degenerative disease that happens when part of the retina called the macula is damaged. It’s the part of the eye that delivers sharp, central vision needed to see objects straight ahead. Over time, the loss of central vision can interfere with everyday activities, such as the ability to drive, read, and see faces clearly.

Diabetes is a complex disease that can result from, genetics, environment, lifestyle factors, such as smoking and diet, and involve systemic diseases like heart disease. How the diabetes develops is not fully understood, but researchers have shown that oxidative stress and inflammation play a critical role in the development and progression of AMD. Drusen formation, the earliest clinical finding, has been shown to result from a localized inflammatory response.

The research on Metformin provides a hope that blindness need not be an eventuality for most people afflicted with diabetes.

Read Original Article:  https://www.sciencedaily.com/releases/2018/10/181029102836.htm