Retinal Pigment Epithelium Stem Cells for AMD Treatment

Loss of retinal pigment epithelial (RPE) cells is a key pathologic feature of age-related macular degeneration (AMD). Human stem cells can be differentiated into functional RPE and show great promise as a new regenerative medicine therapy to prevent vision loss in people with AMD. Dr. Lin’s team proposes research to develop a new source of stem cells that are naturally present within the human eye as a source of RPE for clinical use in patients with AMD.

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly with no effective cures for geographic atrophy, an advanced form of dry AMD. Death of RPE causes both dry and wet AMD. RPE transplantation can restore vision in animal models of retinal degeneration. In people, RPE transplantation has been hindered by a scarcity of safe sources of abundant, healthy human RPE. Here, Dr. Lin proposes to generate RPE from RPE Stem Cells (RPESCs) isolated from human eyes. RPESCs are a newly described type of adult stem cell population that comprises ~2-10% of cells in the primary RPE monolayer and can be isolated from human eyes and generate functional RPE in animal models. Unlike other stem cells, RPESCs do not need the addition of growth-promoting genes or viruses to produce RPE. Therefore, RPESCs may provide a new source of safe, abundant RPE for AMD therapies. A limiting factor in getting RPESCs is obtaining a healthy source of donor human eyes from which to obtain the cells.

In this project, Dr. Lin’s team will use healthy human eyes available from their medical center to develop RPESCs for cell-replacement therapy. Specific Aims include: 1. Isolate primary RPE and RPESCs from donors from diverse background demographics. 2. Compare the functional properties of primary RPE vs. RPESC-derived RPE. Completion of this project will result in the identification of RPESCs that produce functional healthy RPE as well as the creation of a large bank of clinically- and molecularly-validated human RPESCs. These new RPESCs may provide a resource for AMD cellular regeneration therapy, where an advantage is that the cells can be HLA-matched (tissue-matched to prevent rejection) for each patient.