Nitric Oxide (NO) Mediates the Inhibition of Form-Deprivation Myopia by Atropine in Chicks

Sci Rep. 2016 Dec 5;6(1):9. doi: 10.1038/s41598-016-0002-7.


Myopia is the most common childhood refractive disorder. Atropine inhibits myopia progression, but its mechanism is unknown. Here, we show that myopia-prevention by atropine requires production of nitric oxide (NO). Form-deprivation myopia (FDM) was induced in week-old chicks by diffusers over the right eye (OD); the left eye (OS) remained ungoggled. On post-goggling days 1, 3, and 5, OD received intravitreally 20 µL of phosphate-buffered saline (vehicle), or vehicle plus: NO source: L-arginine (L-Arg, 60-6,000 nmol) or sodium nitroprusside (SNP, 10-1,000 nmol); atropine (240 nmol); NO inhibitors: L-NIO or L-NMMA (6 nmol); negative controls: D-Arg (10 µmol) or D-NMMA (6 nmol); or atropine plus L-NIO, L-NMMA, or D-NMMA; OS received vehicle. On day 6 post-goggling, refractive error, axial length, equatorial diameter, and wet weight were measured. Vehicle-injected goggled eyes developed significant FDM. This was inhibited by L-Arg (ED50 = 400 nmol) or SNP (ED50 = 20 nmol), but not D-Arg. Higher-dose SNP, but not L-Arg, was toxic to retina/RPE. Atropine inhibited FDM as expected; adding NOS-inhibitors (L-NIO, L-NMMA) to atropine inhibited this effect dose-dependently, but adding D-NMMA did not. Equatorial diameter, wet weight, and metrics of control eyes were not affected by any treatment. In summary, intraocular NO inhibits myopia dose-dependently and is obligatory for inhibition of myopia by atropine.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Arginine / therapeutic use
  • Atropine / adverse effects
  • Atropine / therapeutic use*
  • Chickens
  • Dose-Response Relationship, Drug
  • Injections, Intraocular
  • Male
  • Myopia / pathology
  • Myopia / physiopathology
  • Myopia / prevention & control*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Donors / therapeutic use*
  • Nitroprusside / pharmacology
  • Nitroprusside / therapeutic use
  • Retina / drug effects
  • Retina / pathology
  • Sensory Deprivation


  • Nitric Oxide Donors
  • Nitroprusside
  • Nitric Oxide
  • Atropine
  • Arginine