Growing evidence suggests that cells linked to regenerating the retina and restoring vision in zebrafish, even after extensive damage, may also hold the key to a cure for blindness in humans.1 Müller glial cells, found in the adult eye, may be developed into a treatment for regenerating damaged human retinas. Müller–cell-based therapies could potentially treat age-related macular degeneration, glaucoma, and diabetic retinopathy—which are responsible for three quarters of registered blindness in the United Kingdom.

In our recent study, my colleagues and I established the existence of immortal Müller cell lines, from several human donor eyes. Because immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. In a research project funded by the Wellcome Trust, the Medical Research Council, and the Helen Hamlyn Trust (all in London), we found that the population of Müller cells that becomes spontaneously immortalized has stem cell properties. These observations confirmed that, like the zebrafish, the adult human retina harbors a population of Müller cells with stem cell characteristics. Because human Müller cells have stem cell characteristics, we were able to develop the cells in vitro into all types of neurons found in the retina. Cells that were grown as adherent monolayers responded to epidermal growth factor and could be expanded indefinitely without growth factors under normal culture conditions. They could be also frozen and thawed without losing their stem cell properties.

TESTED IN RAT MODELS
When tested in rat models with diseased retinas, we found that the cells migrated into the retina and expressed the markers of neurons present in the region where they migrated. This expression suggests that these cells may have potential use for cell-based therapies to restore retinal function.

We are currently growing the cells in the lab and transplanting them into various animal models of retinal disease to identify the best methods for potential transplantation into humans. We are also looking for ways to stimulate growth and persuade the eye to repair itself, using its own cells.

POTENTIAL TO RESTORE VISION
Müller cells with stem cell properties could potentially restore vision to someone who is losing, or has lost his or her sight due to retinal disease or damage. It might be possible to use cells from a person’s own eye, which means that there is less chance of the body rejecting the treatment. It also may be possible to grow cells from donor eyes and store them in a cell bank for transplantation to other individuals subject to tissue compatibility testing (much like we already do for kidney and heart transplants).

Although Müller glial cells with stem cell characteristics are present in the human eye, it is not clear why these cells do not automatically repair the diseased retina. It is possible that internal mechanisms exist in the normal adult retina and prevent these cells from dividing and replicating. Our next step is to identify which factor is responsible for blocking the regeneration. Once we know how this mechanism works, we will be closer to developing alternative treatments to transplantation.

We hope that a transplantation treatment will be possible within the next 5 to 10 years, for cells isolated from a person’s own eye. The second approach of transplanting donor cells will take longer, as we also need to overcome the immune response.

G. Astrid Limb, BSc, MSc, PhD, is Helen Hamlyn Principal Research Fellow and group leader of the retinal regeneration group of the Ocular Repair and Regeneration Biology Unit, at the University College London. Dr. Limb states that she has no financial interest in the products or companies mentioned. She may be reached at g.limb@ucl.ac.uk.

1. Lawrence JM, Singhal S, Bhatia B, et al. MIO-M1 cells and similar Müller glial cell lines derived from adult human retina exhibit neural. Stem Cells. 2007;8:2033-2043.