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New publication: Using nicotinamide to treat glaucoma

Writer's picture: Raymond WongRaymond Wong

Updated: Jul 14, 2023

In collaboration with scientists Karolinska Institutet (Sweden), the team has showed that human retinal ganglion cells can directly utilize nicotinamide and could maintain a capacity to do so in glaucoma, showing promise for ongoing clinical trials targeting NAD for glaucoma treatment.


NAD salvage pathway machinery expression in normal and glaucomatous retina and optic nerve


James R. Tribble, Anna Hagström, Kenza Jusseaume, Emma Lardner, Raymond Ching-Bong Wong, Gustav Stålhammar & Pete A. Williams


Acta Neuropathologica Communications, volume 11, Article number: 18 (2023)




Abstract


Glaucoma is the leading cause of irreversible blindness and is a major health and economic burden. Current treatments do not address the neurodegenerative component of glaucoma. In animal models of glaucoma, the capacity to maintain retinal nicotinamide adenine dinucleotide (NAD) pools declines early during disease pathogenesis. Treatment with nicotinamide, an NAD precursor through the NAD salvage pathway, robustly protects against neurodegeneration in a number of glaucoma models and improves vision in existing glaucoma patients. However, it remains unknown in humans what retinal cell types are able to process nicotinamide to NAD and how these are affected in glaucoma. To address this, we utilized publicly available RNA-sequencing data (bulk, single cell, and single nucleus) and antibody labelling in highly preserved enucleated human eyes to identify expression of NAD synthesizing enzyme machinery. This identifies that the neural retina favors expression of the NAD salvage pathway, and that retinal ganglion cells are particularly enriched for these enzymes. NMNAT2, a key terminal enzyme in the salvage pathway, is predominantly expressed in retinal ganglion cell relevant layers of the retina and declines in glaucoma. These findings suggest that human retinal ganglion cells can directly utilize nicotinamide and could maintain a capacity to do so in glaucoma, showing promise for ongoing clinical trials.


Read the publication here.

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