UC San Diego

Retinal neuron degenerations of an eye can result in permanent photoreceptor or retinal ganglion cell loss which leads to permanent blindness. One potential approach to restore vision loss is through transplanting stem cell or stem cell-derived retinal neurons into the sub-retinal space of the injured retina. However, these transplanted cells often fail to integrate or form a functional connections with the neighboring retinal neurons. Another alternative approach is referred to as the endogenous regeneration whereby new retinal neurons are generated from Müller glia to replace those lost photoreceptors and retinal ganglion cells. Müller glia is the only cell in the retina that shares a common origin with retinal neurons. Thus it has the potential to convert into retinal neurons. Studies have shown that Müller cells in fish, amphibians, and chickens in early developmental stage respond to injury, triggering in vivo regeneration of retinal neurons. In mammals this form of regeneration is less common but does appear to occur as well, however, it remains to be determined whether human Müller glia can dedifferentiate into retinal progenitor and regenerate retinal neurons. Therefore, my project aims to establish Müller cell specific fluorescent reporter systems to aid in future Müller Glia endogenous studies. One approach is to build a dual reporter system that tags both retinal ganglion cells and Müller Glia, tracking the exact time point at which Müller cells are developed from iPSCs. The other approach is to use a lineage tracing system and permanently tag Müller cells once they are born. The advantage of the lineage tracer system is that even if Müller cells convert into other cell types, the fluorescent markers will continue to be expressed, therefore indicating their Müller Glia origin.