Human Limbal Epithelial Stem Cell Conversion into Photoreceptors for Treatment of Retinal Degeneration

Funding Type: 
New Faculty II
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Few people know that age-related macular degeneration (AMD) is the leading cause of blindness of people over 55 in the US. More than 10 million Americans are affected by this irreversible disease and the risk of getting macular degeneration reaches nearly 30 percent in those over age 75. Former Director of the National Eye Institute publicly stated that AMD will soon take on aspects of an epidemic.
The disease affects the central part of the retina – light-sensitive tissue located inside the eye. Retina is a multilayer tissue that contains light-perceiving neuronal cells called photoreceptors. These cells are connected to other neurons in the retina that process the image information and send it to the brain via the optic nerve.
The destruction of photoreceptors and supporting retinal cells is progressive in AMD and no effective therapy to recover lost vision exists. Ophthalmologists can slow down abnormal vessel growth and scarring, but replenishing lost retinal cells to recover vision is not yet possible.
The discovery of stem cells opened new possibilities to rebuild aging and damaged tissues throughout the body. We propose a procedure by which to convert stem cells present on the surface of the eye into light-perceiving neurons. These stem cells are present in a ring-shaped structure located on the front surface of the eye around the cornea. This structure, called limbus, is an active factory where stem cells convert into surface cells used to cover the cornea and lost as we blink. These multipotent stem cells have the same origin as the internal stem cells that become retina during eye development, and have the same latent neuronal program that can be activated. Stem cells in general conform to the environment of the organ they live in and follow the commands of the “niche”, the surroundings, to differentiate into specialized cells needed at that particular location. We propose to take stem cells from the limbus and free them from their niche, provide stimulants and growth factors that signal the need for nerve cells, and allow them to grow into photoreceptors. We then intend to transplant these new photoreceptors into retina and stimulate their integration and activation of light perception. Many parts of this research have already been successful in mice.
For our research we plan to use part of human tissue donated to eye banks for corneal transplantation that is currently being discarded after surgery, thus avoiding many ethical and technical issues associated with other stem cell use. We plan to develop a therapy where a small amount of eye surface tissue from a patient is grown and converted into photoreceptors and given back to the same patient, avoiding problems of rejection and immunosuppression. This revolutionary therapy will make it possible to restore vision in people with macular degeneration.

Statement of Benefit to California: 

Age-related macular degeneration is promising to become a very significant health problem and public burden by year 2025. Given lack of a therapy with the potential to return lost vision to the patients with this disease at the present time, human suffering due to blindness caused by AMD is already alarming many ophthalmologists such as myself. The State of California will benefit immensely from this breakthrough research and subsequent novel therapy, in both human and fiscal aspects. The availability of therapy to restore retinal structures will reinforce California's leadership position in stem cell research and regenerative medicine. Potential for commercialization of this therapy and making it available to millions of people would bring significant private funding resulting in significant revenue and growth of stem cell biotechnology sector. Further extension of findings of this project to other tissues, especially other parts of nervous system, can amplify these beneficial effects several times over. Successful therapy for the most common blinding disease of aging population of the State of California would also significantly decrease healthcare and social care burden while improving the quality of life for the patients.