(175g) Retinal Progenitor Cell Differentiation By Electrical Stimulation on Microcircuit Interfaces

Vision loss and blindness affect an estimated 7 million people in America. Retinal degenerative disease is the leading contributor to vision loss and blindness. The retina is composed of complex layered neural tissue composed of retinal ganglion, amacrine, bipolar, horizontal, rod and cone photoreceptors, Müller glial cells and astrocytes, which must all work in conjunction to transduce light into meaningful electrical signals. Many retinal degenerative diseases, including age-related macular degeneration, glaucoma, and retinitis pigmentosa, all result in cell loss leading to vision impairment or blindness. The unique irreversibility of retinal degeneration has made it a critical target for stem cell-based therapies. There is a need to investigate robust methods of directing differentiation of cost-effective external progenitor cell lines to address the morphology, functionality, and cell specificity required for transplantation treatment. Our previous work has demonstrated the ability to transdifferentiate adult bone marrow-derived mesenchymal stem cells to neural cells using electrical stimulation. In this study, we are developing flexible, biodegradable, and implantable microcircuit interfaces to control the differentiation and fate commitment of murine retinal progenitor cells (RPCs) via electrical stimuli. RPCs are self-renewing, multipotent central nervous system progenitors that give rise to the retina during development. Tunable substrates for electrical stimulation provide a desirable microenvironment for cellular attachment, growth, and migration while conductive graphene circuits enable local control of the electrical field. We have used novel microfluidics and polymer casting-based graphene transfer methods to fabricate degradable and flexible polymer substrates with electronic interfaces. Specifically, this work implements a 3D-printed interdigitated capacitor to electrically stimulate RPCs. Immunocytochemistry with a panel of cell type specific antibody markers is used to evaluate the molecular and morphological differentiation of the RPCs following electric stimulation. The data generated can then be used to assess the resulting differentiated state, for robust control of stem cell differentiation.