Cones derived from human stem cells help mice See: Study

R.Researchers report that they used human stem cell-derived retinal cone photoreceptors to restore vision in mice with advanced retinal degeneration. They are currently planning a clinical trial to test whether transplanting healthy cone photoreceptors into people with age-related macular degeneration improves their eyesight.

Other studies have transplanted stem cell-derived retinal cells into patients with macular degeneration, but this latest work on mice transplanted cone photoreceptors rather than retinal pigment epithelium.

“The reason we focus on cones is because they’re most important to human vision,” says Robin Ali, who is studying Cell and Gene Therapy at King’s College London and who led the study, which appeared April 20 Cell reports. Ali contrasts the role of cones, which allow us to recognize colors, recognize other people’s faces and see them in a brightly lit room, with that of rods, a kind of photoreceptor that works in low light and helps with peripheral vision . While people with rod degeneration may have tunnel vision, people with cone degeneration can become completely blind, Ali says.

The most common eye disease associated with cone decay is macular degeneration. “When you’re old enough, you have some form of macular degeneration,” says Ali. Ophthalmologists can sometimes slow the progression of the disease, but they still cannot reverse the visual decline.

Ali and colleagues wanted to know if stem cells differentiated into cone photoreceptors could restore some level of vision in mice with inactive cones. They developed two variants of human cones: one made from embryonic stem cells that worked and looked normal, and a control type that appeared normal but could not respond to light. These control cones were obtained from the peripheral blood of a 40 year old person with achromatopsia, a disease that results in partial or complete loss of color vision.

Ali’s team transplanted the cones into the retinas of mice bred to develop an advanced eye disease with completely dysfunctional cones. The use of these mice controlled the possibility that residual function from existing cones, rather than newly transplanted cones, was responsible for any improvement in vision. To ensure that the mice did not develop immune defenses against the human cells, they were also bred to be immunodeficient.

The researchers injected functional cones into the retina of 32 mouse eyes and the aberrant cones into another 23 eyes. Sometimes both eyes of a mouse received the transplants, sometimes only one. Both types of cones, whether they worked or not, adhered to the retina and formed a mass of cells typical of healthy eyes and necessary for seeing in bright light.

However, the similarities ended when the researchers exposed the mice to the light. The retinas of mice with functional human cones responded to light during an eye test called a microelectroretinogram, while the retinas of mice with dysfunctional cones did not. In another test, the mice that received the functional cones withdrew to a dark room of their choice, an indication that the nocturnal animals perceived the light and avoided it, as mice normally do. In contrast, mice with deficient cones stayed in the light most of the time.

“I’m just impressed with the study. The kind of checks these authors have done – the effort they have put into making sure it was a complete, pure response to the transplanted cells are just amazing, ”says Hemant Khanna, ophthalmologist at the medical Faculty of the University of Massachusetts that did not participate in the project. Khanna believes this study will set a new bar for experimental design that similar works will have to accomplish in the future.

“It took us twenty years to actually get to the point of this study, which I’m very excited about,” says Ali, calling it a proof of concept that transplanted cones have the ability to improve eyesight. While Ali notes that the capacity to manufacture cones on a large scale is not yet in place, he is confident that his laboratory can produce enough cones for a human clinical trial. His next step is to recruit 16 participants in the UK over the next few years.

Ophthalmologist Sai Chavala of the University of North Texas Health Science Center points out that one problem with a stem cell-derived transplant is that it can take a while for stem cells to mature into cells to be transplanted. In a 2020 study in nature, Chavala and colleagues showed that it is possible to convert mouse skin cells directly into photoreceptors that can be transplanted into the retina of mice, rather than first converting the skin cells into induced pluripotent stem cells. In this study, the skin cells were converted into rods rather than cones.

J. Ribeiro et al., “Restoration of Visual Function in Advanced Disease After Transplantation of Purified Human Pluripotent Stem Cell-Derived Cone Photoreceptors”. Cell Rep, doi: 10.1016 / j.celrep.2021.109022, 2021.



Source link

Posted in Science

Leave a Comment

Thanks for visiting get comfortable with the space, officially registering is the most important thing to do right now The first big project won’t start until your on board.