In a controversial new study published on August 15 in Nature, scientists claim they have induced cells of the retina ― Müller glia ― to regenerate light receptor cells allowing mice to detect incoming light and form a communication network with other cells in the eye to pass signals to the brain. The study represents a potential step toward reversing certain genetic eye conditions and injury.
Photoreceptors are specialised nerve cells found in the retina ― a thin layer of tissue lining the back of the eye ― and are responsible for converting incoming light into electrical signals. Damage to these cells, resulting from ageing and disease, can affect vision and may eventually lead to blindness. In fish and amphibian eyes, Müller glia can divide and replace damaged photoreceptor cells but unfortunately, the rods and cones of mammals do not regenerate on their own once damaged. Mammalian Müller cells simply provide support and nourish surrounding cells, occasionally regenerating photoreceptor cells after injury, but only a relatively small number of them.
Scientists are attempting to rejuvenate the self-repair mechanisms of the mammalian retina to treat retinal disorders, which would be a less-invasive approach compared to the stem cell treatments currently being tested in the clinic (2). Prof Bo Chen, a neuroscientist at the Icahn School of Medicine at Mount Sinai in New York City, and his colleagues have managed to restore vision in mice born with congenital blindness by using gene transfer to reprogram Müller glia into functioning photoreceptors.
In this work, the gene transfer process was broken up into two stages. The first involved injecting a gene into the eyes of healthy mice that switches on a protein called beta-catenin and stimulates Müller glia to start dividing. After a few weeks, additional factors were injected into the eye in order to stimulate the newly-divided cells to develop into photoreceptor rods. Müller glia generated using this process appeared to be exactly the same as the natural versions and a network of synapses was also established, enabling the newly formed cells to communicate with other neurons in the retina.
Researchers then attempted the procedure in congenitally blind mice, which still have rods and cones but lack two of the key genes that enable photoreceptors to transmit signals. When exposed to light, treated mice showed activity in part of the brain that receives visual signals. Based on the results, the research team concluded that the new rods had become part of the retinal cell signalling network and were able to successfully transmit information to the brain. Further testing is needed to examine how well mice now perform visual tasks and to determine whether the treatment can be applied with the same success to human retinal cells.
Some experts are sceptical arguing that the signals may have come from existing photoreceptor cells in the eye. However, according to Science, Chen maintains that they have thoroughly demonstrated the origin of the new photoreceptor rods via several methods.
Gene therapy is showing promise in many areas of human health and could potentially be used to restore vision in those with a detached retina or retinitis pigmentosa ― a genetic disorder ― or for treating age-related macular degeneration.
(1) Yao, K. et al. Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas. Nature (2018). DOI: 10.1038/s41586-018-0425-3
(2) Kashani, A.H. et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Science Translational Medicine (2018). DOI: 10.1126/scitranslmed.aao4097