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 infection in contact lens wearers due to poor hygiene can cause blindness

There are reports of an outbreak of a rare but essentially preventable eye infection that can cause blindness, identified in contact lens wearers in a new study led by UCL and Moorfields Eye Hospital researchers. The research team found a threefold increase in Acanthamoeba keratitis since 2011 in South-East England.

The findings showed that reusable contact lens wearers with the eye infection were more likely to have used an ineffective contact lens solution, have contaminated their lenses with water or reported poor contact lens hygiene. “This infection is still quite rare, usually affecting 2.5 in 100,000 contact lens users per year in South East England, but it’s largely preventable. This increase in cases highlights the need for contact lens users to be aware of the risks,” said the study’s lead author, Professor John Dart (UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust).

Acanthamoeba keratitis is an eye disease that causes the front surface of the eye, the cornea, to become painful and inflamed, due to infection by Acanthamoeba, a cyst-forming microorganism.

The most severely affected patients (a quarter of the total) have less than 25% of vision or become blind following the disease and face prolonged treatment. Overall 25% of people affected require corneal transplants to treat the disease or restore vision.

Anyone can be infected, but research shows that contact lens users face the highest risk, due to a combination of increased exposure to infection, for reasons not fully established, as a result of contact lens wear and contamination of lens cases.

Alongside these findings, they conducted a case-control study of people who wear reusable contact lenses on a daily basis (although the disease is also associated with disposable lenses), comparing those who had a diagnosis of Acanthamoeba keratitis to those who had come in to Moorfields A&E for any other reason, from 2011 to 2014.

The case-control study included 63 people with Acanthamoeba keratitis and 213 without. They all completed a questionnaire, from which the researchers found that the risk of developing the disease was more than three times greater amongst people with poor contact lens hygiene, people who did not always wash and dry their hands before handling their lenses, those who used a lens disinfectant product containing Oxipol (now phased out by the manufacturer), and for people who wore their contacts while in swimming pools or hot tubs. Showering and face washing while wearing contact lenses are also likely to be risk factors.

Acanthamoeba is more commonly found in the UK than in other countries, likely due to higher levels found in domestic (as opposed to mains) water supplies, so that water contamination of contact lenses is of particular concern in the UK.

The researchers say the current outbreak is unlikely to be due to any one of the identified risk factors in isolation.

“People who wear reusable contact lenses need to make sure they thoroughly wash and dry their hands before handling contact lenses, and avoid wearing them while swimming, face washing or bathing. Daily disposable lenses, which eliminate the need for contact lens cases or solutions, may be safer and we are currently analysing our data to establish the risk factors for these,” said Professor Dart.

To read to original article in its entirety, click here. https://www.sciencedaily.com/releases/2018/09/180921082952.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