Study of Human Retinal Ganglion Cell Development and Direct Conversion

The loss of retinal ganglion cells (RGCs) causes irreversible vision loss in glaucoma and optic neuropathies. Some vertebrate species, such as zebrafish, possess a robust ability to regenerate parts of their body, including the retina through a process of endogenous regeneration. However, this ability is limited in mammals including humans. To understand endogenous regeneration and work towards restoring RGCs, we need to gain a better understanding of the developmental mechanisms leading to RGC formation. Our approach relies on the generation of RGC reporters that express fluorescent proteins coupled to the endogenous BRN3A and BRN3B genes. By ectopically overexpressing four transcription factors (Neurogenin-2, Atonal homolog 7, Islet-1, and Brn3b) involved in RGC specification and differentiation, we seek to directly convert the human pluripotent stem cell reporters into RGCs. If the differentiated neurons become bonafide BRN3A/BRN3B expressing RGCs, this would represent an important first step in developing and improving novel therapeutic strategies for retinal diseases