Stem cells and nerve cell renewal in glaucoma G. Astrid Limb

Anatomy of the Eye Retinal Nerve cells

Nerve cells of the Retina Nerve cells extend to the optic nerve that connects to the brain Damage to nerve cells of the retina causes vision impairment

The zebrafish regenerate retina throughout life Fish can grow a new retina and regain vision after extensive damage. Cells found in the fish eye, known as Müller cells, are responsible for this regeneration.

The adult human retina contains Müller stem cells Spheres in culture dishes Müller stem cells They can be induced to become nerve cells in the laboratory

Characteristics of ‘Stem cells’ Self renewal (immortal) Potential to develop into many cell types Are capable of repairing the body They can divide to remain as stem cells, but they also specialize to become other cells such as blood cells, brain or retinal cells

Research approaches to regenerate the retina Stem cells : They can be derived from embryos, adult human tissues (including the eye), or can be produced in the laboratory using the patient’s own cells. Gene therapy: Genes that induce production of nerve protection factors are being investigated for their use in glaucoma therapies.

Potential approaches to regenerate the retina Self repair: Since the human eye has its own stem cells, it might be possible to induce ‘dormant’ cells to become active and generate new nerve cells to replace the damaged ones.

Potential advantages of adult stem cells: Avoid problems of identification of organ specific stem cells and donor availability. Cells for grafting could be obtained from our own tissue, preventing ethical and practical problems arising from the use of embryonic cells.

Only Current research in stem cells Evidence of success in rodents. The anatomy of the human eye is different from rodents, so more research is needed to develop methods that can be used in the human eye. There is the need to prepare cells under pharmaceutical conditions. This might take a few years before they can be tested in humans. In the real situation we will encounter not an intact-permissible environment, but damaged tissue with lack of function and in need of repair.

Only Current research in stem cells It is possible that transplanted cells are rejected by the body’s immune system. Therefore long term immune suppression with drugs might be necessary, like any organ transplant. However, if these barriers are overcome, stem cell transplantation may significantly improve visual function in patients for whom other treatments are not available.

Self repair (endogenous regeneration) At present there is Scientific interest to investigate small molecules (drugs) that could induce stem cells present in the adult retina to grow and replace damaged nerve cells. This process, known as ‘endogenous regeneration’ may involve repeated injections of drugs into the eye. Ideally this method would avoid the need for stem cell transplantation, but much research is needed.

Acknowledgements Institute of Ophthalmology and Moorfields Eye Hospital Jean Lawrence Shweta Singhal Bhairavi Bhatia James Ellis Tony Kwan David Keegan Philip Luthert Michael Sheldom Daniel Tadman Christina Guo Aaron Wong Ismay Humphries Lund University, Sweden Maria Thereza Perez Cambridge University James Fawcett Keith Martin University of Washington Tom Reh Present team: Sir Peng T Khaw Hari Jayaram David Charteris Silke Becker Megan Jones Karen Eastlake Angshu Angbohang