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Peer-reviewedCC BY 4.0Scientific Reports

Systemic influences of dietary NAD+ supplementation relevant to the search for ocular hypertensive therapies for glaucoma

4 affiliations
  1. 1Department of Molecular Physiology and Biophysics, University of Iowa, 375 Newton Road, Iowa City, IA 52242 USA
  2. 2Institute for Vision Research, University of Iowa, Iowa City, IA USA
  3. 3Department of Biostatistics, University of Iowa, Iowa City, IA USA
  4. 4Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA USA

Abstract

Dietary nicotinamide (NAM) is neuroprotective in rodent models of glaucoma. With dietary delivery, additional systemic influences of NAM are possible, prompting us to test for influences on non-neuronal phenotypes relevant to glaucoma. Test cohorts of mice on high-fat diets differed by NAM content (control, “CON-diet”; 2,000 mg/kg/day supplementation, “NAM-diet”) and by ocular treatments inducing various levels of ocular hypertension (Naïve; Ad5-Empty; Ad5-ATF4). Masked observers assessed intraocular pressure (IOP), body weight, and slit-lamp appearance. Naïve and Ad5-Empty cohorts were analyzed for gut microbiome composition. Regardless of diet, Naïve cohorts maintained consistent IOP. On CON-diet, the Ad5-ATF4 and Ad5-Empty cohorts developed IOP elevation. Based on results from a linear mixed-effects model evaluating the effects of diet and ocular treatment on IOP, NAM-diet lowered IOP in only the Ad5-Empty cohort. NAM-diet also prevented weight gain associated with a high-fat diet. NAM-diet was linked to altered alpha and beta diversity of the gut microbiome, including changes to a butyrate-producing genus, Faecalibaculum. Among the systemic influences resulting from dietary NAM consumption, NAM’s ability to affect both neuroprotection and IOP would be favorable for glaucoma therapy. The possibility of dietary NAM influencing body weight and microbiome composition in humans warrants additional investigation.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-58123-8.

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BibTeX
@article{meyer2026systemic,
  title = {{Systemic influences of dietary NAD+ supplementation relevant to the search for ocular hypertensive therapies for glaucoma}},
  author = {Kacie J. Meyer and Adam Hedberg-Buenz and Kai Wang and Michael G. Anderson},
  journal = {Scientific Reports},
  year = {2026},
  month = jul,
  doi = {10.1038/s41598-026-58123-8},
  url = {https://doi.org/10.1038/s41598-026-58123-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Systemic influences of dietary NAD+ supplementation relevant to the search for ocular hypertensive therapies for glaucoma
AU  - Kacie J. Meyer
AU  - Adam Hedberg-Buenz
AU  - Kai Wang
AU  - Michael G. Anderson
PY  - 2026
DA  - 2026/07/29
JO  - Scientific Reports
DO  - 10.1038/s41598-026-58123-8
UR  - https://doi.org/10.1038/s41598-026-58123-8
AB  - Dietary nicotinamide (NAM) is neuroprotective in rodent models of glaucoma. With dietary delivery, additional systemic influences of NAM are possible, prompting us to test for influences on non-neuronal phenotypes relevant to glaucoma. Test cohorts of mice on high-fat diets differed by NAM content (control, “CON-diet”; 2,000 mg/kg/day supplementation, “NAM-diet”) and by ocular treatments inducing various levels of ocular hypertension (Naïve; Ad5-Empty; Ad5-ATF4). Masked observers assessed intraocular pressure (IOP), body weight, and slit-lamp appearance. Naïve and Ad5-Empty cohorts were analyzed for gut microbiome composition. Regardless of diet, Naïve cohorts maintained consistent IOP. On CON-diet, the Ad5-ATF4 and Ad5-Empty cohorts developed IOP elevation. Based on results from a linear mixed-effects model evaluating the effects of diet and ocular treatment on IOP, NAM-diet lowered IOP in only the Ad5-Empty cohort. NAM-diet also prevented weight gain associated with a high-fat diet. NAM-diet was linked to altered alpha and beta diversity of the gut microbiome, including changes to a butyrate-producing genus, Faecalibaculum. Among the systemic influences resulting from dietary NAM consumption, NAM’s ability to affect both neuroprotection and IOP would be favorable for glaucoma therapy. The possibility of dietary NAM influencing body weight and microbiome composition in humans warrants additional investigation.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-58123-8.
SN  - 2045-2322
ER  -