Developing Autologous Cell Therapy for Age-related Macular Degeneration using Patient-specific Induced Pluripotent Stem Cell derived Retinal Pigment Epithelium

Abstract

Purpose : Age-related macular degeneration (AMD) is one of the leading causes of blindness among elderly. Advanced disease stage with the death of photoreceptors and vision loss is initiated by the atrophy of retinal pigment epithelium (RPE), a monolayer of cells in the back of the eye. It is thought that RPE replacement will protect overlying photoreceptors from dying and preserve vision in AMD patients. Here we develop an autologous cell therapy for AMD using an RPE patch developed from patient-specific induced pluripotent stem (iPS) cells.

Methods : iPS cells are derived using a xeno-free, integration-free process and RPE cells are differentiated using a developmentally guided differentiation protocol. RPE patch is created on biodegradable clinical-grade and biocompatible PLGA scaffold. RPE patch functionality is confirmed by phagocytosis of photoreceptor outer segments (POS), polarized cytokine secretion, and electrophysiological measurements. Laser-induced RPE injury in pigs is used to create RPE atrophy and photoreceptor degeneration. Standard vitrectomy procedure is used to deliver RPE patch underneath the retina. Optical coherence tomography and multi-focal ERG is used to evaluate RPE patch in the sub-retinal space.

Results : Our clinicial-grade RPE patch from AMD patients is able to phagocytose POS, secrete VEGF and PEDF in a polarized fashion, and demonstrates electrophysiology properties that similar to native human RPE. Laser injury results in RPE cell death followed by photoreceptor degeneration in the pig model. Transplanted human RPE patch rescues photoreceptor degeneration in this laser-induced RPE injury model.

Conclusions : We have developed an efficient and reproducible clinical-grade manufacturing process to develop iPS cell derived RPE patch from three AMD patients. Human RPE patch is laser-injured pig eyes in able to rescue photoreceptors from degenerating. This data provides proof-of-principle data for IND-enabling studies for a phase I clinical trial to test this potential autologous cell therapy in AMD patients.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.