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Supplemental nitrite increases choroidal neovascularization in mice.

Xiaoping Qi1, Karina Ricart2, Khandaker A Ahmed2

  • 1Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, AL, 35294, USA.

Nitric Oxide : Biology and Chemistry
|September 19, 2021
PubMed
Summary

Low doses of nitrite and nitrate, commonly found in supplements and vegetables, significantly increased choroidal neovascularization (CNV) lesions in mice. This suggests caution for nitrite/nitrate supplementation in elderly individuals susceptible to age-related macular degeneration (AMD).

Keywords:
Age-related macular degenerationAgingChoroidal neovascularizationNitrateNitrite

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Area of Science:

  • Ophthalmology
  • Vascular Biology
  • Pharmacology

Background:

  • Nitrite, at physiological levels, enhances blood flow via nitric oxide (NO).
  • Nitrite therapy and nitrate-rich vegetable consumption (e.g., beets) are increasingly popular.
  • Choroidal neovascularization (CNV) is a hallmark of wet age-related macular degeneration (AMD).

Purpose of the Study:

  • To investigate the impact of low-dose nitrite and nitrate supplementation on the development of CNV.
  • To assess age-related differences in CNV lesion volume.
  • To evaluate the safety of nitrite and nitrate supplementation in the context of AMD.

Main Methods:

  • C57BL/6J mice (2 and 12 months old) received sodium nitrite, nitrate, or water for one week.
  • Laser-induced CNV (L-CNV) was performed, followed by 14 days of continued supplementation.
  • CNV lesion volume was quantified using optical coherence tomography (OCT); plasma and eye tissues were analyzed.

Main Results:

  • Both nitrite (300 mg/L) and nitrate (1 g/L) significantly increased CNV lesion volume in young and older mice compared to controls.
  • Older mice exhibited larger baseline CNV volumes than younger mice.
  • Plasma nitrite levels increased in young mice receiving nitrite, while plasma nitrate increased in older mice receiving nitrite and in both age groups receiving nitrate.

Conclusions:

  • Oral nitrite and nitrate supplementation, even at low doses, exacerbate choroidal neovascularization (CNV) in a mouse model.
  • Age is a significant factor, with older mice showing larger CNV lesions.
  • Caution is advised regarding the use of nitrite and nitrate supplements, particularly in elderly individuals at risk for AMD.