Fig. 1

NAD synthesis pathways are represented in the retina. A NAD is synthesized through 3 pathways: the NAD salvage pathway, the Preiss-Handler pathway, and de novo from tryptophan. The salvage pathway (red) converts nicotinamide (NAM, a main dietary from of vitamin B₃; also known as niacinamide) to NAD⁺ in a two-step reaction. NAM is converted to nicotinamide mononucleotide (NMN) by the enzyme NAMPT, which is then converted to NAD⁺ by NNMNATs (isoforms 1–3 are expressed in different cells and localize to different cellular compartments). Alternatively, nicotinamide riboside (NR) can be converted to either NAM (by the enzyme PNP) or NMN (by the enzyme NMRK, isoforms 1–2). NAD⁺ is recycled to NAM by NAD consumers, allowing cells to replenish NAD without constant influx of dietary precursors. The Preiss-Handler pathway (blue) converts nicotinic acid (NA; also known as niacin) to NAD⁺ in a three-step reaction. NA is converted to nicotinic acid mononucleotide (NAMN) by the enzyme NAPRT, which is converted to nicotinic acid adenine dinucleotide (NAAD⁺) by NNMNATs, and finally to NAD⁺ by the enzyme NADSYN1. Tryptophan can be converted to NAD⁺ through de novo synthesis (magenta) involving the kinurenine pathway (a six-step reaction which generates NAMN). Enzymes are shown as gene names (HGNC). B Gene expression of NAD-synthesizing enzymes was examined in publicly available bulk sequenced mRNA in 105 whole human retina. NAD-salvage pathway transcripts are well expressed (expect for the NMRK2 isoform). NAPRT in the Preiss-Handler pathway is lowly expressed, whereas NADSYN1 is well expressed suggesting that the retina may favor the NAD-salvage pathway