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<p>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&#xa0;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, <i>Faecalibaculum</i>. 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Kacie J. Meyer,
  • Adam Hedberg-Buenz,
  • Kai Wang,
  • Michael G. Anderson

摘要

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.