Stem Cell-Derived Retinal Pigment Epithelial cells for Treatment of Age-Related Macular Degeneration and Retinitis Pigmentosa

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

Age-related macular degeneration (AMD) and Retinitis Pigmentosa (RP) are leading causes of vision loss with no effective cures. Death of Retinal Pigment Epithelium (RPE) in the eye causes AMD and RP. RPE transplantation can restore vision in animals. In people, RPE transplantation has been hindered by lack of healthy human RPE and concerns about whether stem cell derived-RPE are safe to use in patients. Here, we will test which RPE-derived stem cells are safest and healthiest by comparing them with the patient's original RPE. Furthermore, we will generate RPE from a new adult stem cell population, Retinal Pigment Epithelial Stem Cells (RPESCs), present in human eyes. To accomplish these goals, we will take advantage of our unique clinical practice in eye pathology, where we receive 100+ human eyes annually for medical evaluation. We will select healthy human eyes, isolate and characterize RPE and RPESCs, and validate if stem cell-derived RPE can match or even outperform the original RPE, as well as isolate new RPESCs from these eyes. Completion of this project will identify which stem cell-derived RPE is safest for patient use and also result in the creation of a large bank of new human RPESCs that can generate large amounts of healthy functional RPE. These findings will provide fundamental safety data for clinical use of stem cell-derived RPE and also offer new regenerative medicine stem cell resources for patients with AMD or RP.

Statement of Benefit to California: 

Age-related macular degeneration (AMD) and Retinitis Pigmentosa (RP) are devastating diseases of the eye that result in progressive loss of vision. Patients with AMD and RP lose the ability to perform life functions including driving, reading, and watching movies or television. These diseases affect a significant number of people, with over 450,000 Californians predicted to suffer from AMD alone by 2020. These diseases place a significant economic burden on patients by interfering with their economic livelihoods. These diseases cause significant public health and safety burdens by increasing chances that patients will be involved in accidents due to visual impairment. AMD and some types of RP are caused by loss of Retinal Pigment Epithelial (RPE) cells in the eye. Many studies have shown that transplantation of healthy RPE can improve visual function, but it has been difficult to get enough healthy human RPE to develop RPE transplantation into a viable therapy to treat AMD and RP. Here, we propose a stem cell based approach to safely generate large amounts of human RPE based on isolating RPE stem cells from human eyes collected from surgical and autopsy donor enucleations. If successful, our strategy would result in the creation of a large bank of diverse donor RPE stem cells whose functional, genetic, and molecular phenotypes would be characterized and then, provided as a new stem cell-based resource for vision restoration therapy in patients with AMD or RP.