Mariana Souza da Silveira, PhD, Federal University of Rio de Janeiro (UFRJ) in Brazil, has been selected to receive the second Larry A. Donoso, MD Award in Retinal Research after receiving the highest ranking score in the 2021 grant review process, a criterion for the Award. The Award was created to honor IRRF Director, Larry A. Donoso, MD, PhD, to recognize his tireless efforts for the IRRF. Dr. Silveira was awarded two-year funding for her proposed project Generation of Induced-Retinal Ganglion Cells by Reprogramming Late Retinal Progenitors and Adult Müller Glia.
Vision loss in glaucoma results from neurodegeneration of retinal ganglion cells (RGCs) and their optic nerve axons, which process and carry visual information from the eye to the brain. RGC loss is irreversible, given that the retina of humans and other mammals lack significant regenerative capacity. However, RGCs effectively regenerate in the adult fish retina from Müller glia (MG). Dr. Silveira is exploring the question, could transcriptional reprogramming of MG reestablish this proliferative and neurogenic ability in the mammalian retina? The identification of reprogramming factors sufficient to override the restriction and promote de novo neurogenesis of RGCs in vivo is key to design novel regenerative strategies for RGC replacement in glaucoma and other conditions that kill these neurons. Two Aims have been identified for this project. Aim 1: Optimize Klf4 (Krüppel-like factor 4) reprogramming strategies of late retinal progenitors to generate mature iRGCs. Aim 2: Establish whether rodent Müller glia can be reprogrammed via Klf4 to generate iRGCs in vivo.
Dr. Silveira will collaborate with Dr. Alejandra Bosco, University of Utah, USA, who will act as co-principal investigator and who will help direct Aim 1 for the project. Dr. Bosco currently works in the laboratory of Monica Vetter, PhD, Chair, Department of Neurobiology at the University of Utah School of Medicine.
Dr. Silveira’s research experience is focused on retinal development. Recently, she started working in reprogramming as an approach for generating a specific cell type, the retinal ganglion cell (RGC).