June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Oral supplementary nicotinamide riboside protects function in a model of inherited mouse glaucoma
Author Affiliations & Notes
  • Ying Li
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Nan Zhang
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Xian Zhang
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Micah A Chrenek
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jiaxing Wang
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jana T Sellers
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Brenner Charles
    Beckman Research Institute, Duarte, California, United States
  • Eldon Geisert
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Ying Li, None; Nan Zhang, None; Xian Zhang, None; Micah Chrenek, None; Jiaxing Wang, None; Jana Sellers, None; Brenner Charles, None; Eldon Geisert, None; Jeffrey Boatright, None
  • Footnotes
    Support  Support funding: VA I01RX002806 (JHB); VA I21RX001924 (JHB); VARR&D C9246C (Atlanta VAMC); Abraham J and Phyllis Katz Foundation (JHB); NIH R01EY028859 (JHB); NIH P30EY06360 (Emory); Owens Family Foundation (EEG); Research to Prevent Blindness (Emory), BrightFocus Foundation G2020286 (JHB&YL).
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2767. doi:
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    • Get Citation

      Ying Li, Nan Zhang, Xian Zhang, Micah A Chrenek, Jiaxing Wang, Jana T Sellers, Brenner Charles, Eldon Geisert, Jeffrey H Boatright; Oral supplementary nicotinamide riboside protects function in a model of inherited mouse glaucoma. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2767.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Purpose: To test whether oral administration of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide ( NAD+) precursor, protects retina ganglion cells (RGCs) from neurodegeneration in the DBA/2J (D2) mouse model of age-related inherited glaucoma.

Methods : Method: NR administration in drinking water (4000mg/kg of body weight per day) started when DBA/2J mice were 9 months old. NR was dissolved in drinking water and changed twice per week, continuing to 13 months old. Control cohort identically received water with no added NR. Intraocular pressure (IOP) was measured every month until experiment completion. Pattern electroretinography (PERG) using a Celeris system (Diagnosys LLC, MA) was recorded before euthanizing mice at 12-13 months old. Retinas were harvested for whole mount immunofluorescence staining with RGC marker Brn3a and imaged by fluorescent confocal microscopy. Retinal NAD+ levels were enzymatically assayed (Abcam, CA).

Results : Results: 13-month-old D2 retinas showed diminished NAD+ concentration compared to 4 months old ones. Our data showed that aged D2 mouse retinal NAD+ level with NR oral supplementary treatment was significantly higher than which from vehicle treatment group. (9.69±1.72 pmol/ul vs 4.24±1.06 pmol/ul, p<0.05, n=6, Mann-Whitney-U test). The amplitude of PERG in NR treatment group (5.05±0.33uV, n=44) was also significantly higher than in vehicle group (3.22uV±0.27, n=34) (p<0.05, t-test). Retinal immunofluorescent Brn3a+ cell counts were significantly higher in NR treatment group than age matched vehicle group (27016.50±3721.17 vs 15114.92±4387.32, n=24, p<0.05, t-test). There was no significant difference in IOP between NR-treated and non-treated eyes at all observation time points from 9 months old up to 12 months old.

Conclusions : Conclusion: NR oral supplementation aids more RGC survival in aged DBA/2J mice, and potentially preserves retinal function via preventing age-dependent NAD+ level decline. The effect of rendering RGCs more resilient to glaucomatous damage in a glaucoma model suggests that NR is worth exploring as a therapeutic candidate in treatment of glaucoma.

This is a 2021 ARVO Annual Meeting abstract.

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