Congenitally blind mice have vision restored

The team from the National Eye Institute (NEI) said the findings would contribute to the development of regenerative therapies for blinding diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).“This is the first report of scientists reprogramming Müller glia to become functional rod photoreceptors in the mammalian retina,” NEI program director for retinal neuroscience Dr Thomas Greenwell said.{{quote-A:R-W:400-I:2-Q:“We wanted to see if we could program Müller glia to become rod photoreceptors in a living mouse without having to injure its retina.”-who:Bo Chen, NEI}}“Rods allow us to see in low light, but they may also help preserve cone photoreceptors, which are important for colour 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.”In mammals, including mice and humans, photoreceptors fail to regenerate on their own as, like most neurons, they don’t divide once they have matured.However, scientists have long studied the regenerative potential of Müller glia because in other species, such as zebrafish, they divide in response to injury. This allows th to turn into photoreceptors and other retinal neurons, meaning zebrafish can regain vision after severe retinal injury.The researchers have been attpting to prompt mammalian Müller glia to behave more like they do in the fish, however 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,” director of the Ocular St Cell Program at Mount Sinai, Associate Professor Bo Chen said.“We wanted to see if we could program Müller glia to become rod photoreceptors in a living mouse without having to injure its retina.”In the first phase of a two-stage 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. Weeks later, they injected the mice’s eyes with factors that encouraged the newly divided cells to develop into rod photoreceptors.The researchers used microscopy to visually track the newly formed cells and found that the newly formed rod photoreceptors looked structurally no different from real photoreceptors. In addition, synaptic structures that allow the rods to communicate with other types of neurons within the retina had also formed. The next phase saw the team treat mice with congenital blindness to determine whether the Müller glia-derived rod photoreceptors were functional.In the treated mice that were born blind, Müller glia-derived rods developed just as effectively as they had in normal mice, while they also were communicating with other types of retinal neurons across synapses.  Furthermore, light responses recorded from retinal ganglion cells and measurents 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 now conducting behavioural studies to determine whether the mice have regained the ability to perform visual tasks, such as a water maze task. They also plan to see if the technique works on cultured human retinal tissue.The study was published in Nature.IMAGE TOP: Artist’s rendering incorporating the images of the Müller glia-derived rod photoreceptors