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Adult human RPE for transplantation: renewing an old promise

Considering the incidence of retinal pigment epithelium (RPE)-related blinding disease will grow to 200 million globally by 2020, the impact of restoring vision by successfully replacing failing or dying RPE is great. In spite of fervent efforts to use primary RPE as a source for transplantation for over 30 years, a clinical therapy has yet to be developed. Due to the progress of pluripotent stem cell technologies and development of RPE differentiation protocols, primary human RPE culture has largely been set aside as a source of RPE for transplantation, as human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived RPE have become the current popular source for transplantation. Recently, a series of seminal advances in human primary RPE culture has renewed an interest in their potential as a source for RPE transplantation. Primary RPE are better studied and understood than hESC/hiPSC-derived RPE, have an inherent lower risk of tumor formation, and can be Major Histocompatibility Complex (MHC) donor-matched, making them valuable candidates alongside pluripotent stem cells as sources for cell transplantation therapy for RPE-related eye diseases. In context Some of the most prevalent blinding diseases, including Age-related Macular Degeneration, Stargardt’s Disease, Retinitis Pigmentosa and others, affect a single epithelial layer in the back of the eye, called the retinal pigment epithelium (RPE). For over the past 40 years, much hope has rested in using adult RPE, for example isolated from cadaver donors, for transplantation, to replace the diseased RPE in affected patients. Critical barriers to this objective are 1. being able to isolate and grow RPE that maintain their physiological and morphological characteristics in vitro and 2. assure successful engraftment and survival of the transplanted cells. What we observed was that often, once dissected, RPE isolated from cadaver donor eyes would change their physiology and not maintain their RPE functions when cultured in vitro. Here we summarize new advances in using adult RPE, which have renewed their promise in treating RPE-related eye diseases.