Lara Rappaport Da Costa Santos
Research Mentor(s): Thanh Hoang
Mentor Department: Ophthalmology and CDB
Authors: Thanh Hoang, Peter Hitchcock, Mikiko Nagashima
Session: Session 4 (1:00pm – 1:50pm)
Presentation Type: Oral
Abstract
Zebrafish possess an extraordinary capacity for tissue regeneration. In the retina of zebrafish, Müller glia serve as the intrinsic stem cells. In response to injury, Müller glia dedifferentiate and generate multipotent progenitor cells that proliferate and differentiate into retinal neurons. Understanding this process could provide insights for developing therapies for human retinal degenerative diseases, such as glaucoma and macular degeneration. Our research focuses on determining how the fate of regenerated neurons is controlled. As a first step, we developed a transgenic lineage tracing line, Tg(mmp9:creERt2; actb2:loxP-dsRed-loxP-eGFP), that allows us to label and track Müller glia-derived regenerated neurons. To examine whether the type of neurons damaged influences the fate of regenerated neurons, transgenic animals were subjected to two injury models: light lesion, which primarily damages photoreceptors, and NMDA injection, which ablates inner retinal neurons. Previous data show that following light lesion, a greater number of photoreceptors are regenerated compared with inner retinal neurons, and following NMDA injection, inner retinal neurons are mostly regenerated. These data suggest that the cell types originally ablated influence the fate of regenerated neurons. We further determined subtypes of regenerated cone photoreceptors and amacrine cells using immunostaining against different cone opsins and antibodies against various neurotransmitters, respectively. Opsin staining confirmed that all four cone subtypes are regenerated after both injury types. Additionally, preliminary data suggest an abundant regeneration of cholinergic amacrine cells, suggesting a potential fate bias in the regenerated amacrine cells.
