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

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