TY - JOUR T1 - Nuclear NAD<sup>+</sup>-biosynthetic enzyme NMNAT1 facilitates survival of developing retinal neurons JF - bioRxiv DO - 10.1101/2021.05.05.442836 SP - 2021.05.05.442836 AU - David Sokolov AU - Emily Sechrest AU - Yekai Wang AU - Connor Nevin AU - Jianhai Du AU - Saravanan Kolandaivelu Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/09/2021.05.05.442836.abstract N2 - Despite mounting evidence that the mammalian retina is exceptionally reliant on proper NAD+ homeostasis for health and function, the specific roles of subcellular NAD+ pools in retinal development, maintenance, and disease remain obscure. Here, we show that deletion of the nuclear-localized NAD+ synthase nicotinamide mononucleotide adenylyltransferase-1 (NMNAT1) in the developing murine retina causes early and severe degeneration of photoreceptors and select inner retinal neurons via multiple distinct cell death pathways. This severe phenotype is associated with disruptions to retinal central carbon metabolism, purine nucleotide synthesis, and amino acid pathways. Furthermore, large-scale transcriptomics reveals dysregulation of a collection of photoreceptor and synapse-specific genes in NMNAT1 knockout retinas prior to detectable morphological or metabolic alterations. Collectively, our study reveals previously unrecognized complexity in NMNAT1-associated retinal degeneration and suggests a yet-undescribed role for NMNAT1 in gene regulation during photoreceptor terminal differentiation.Competing Interest StatementThe authors have declared no competing interest. ER -