July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Atropine and NO inhibit form-deprivation myopia via retinal mechanisms in the chick
Author Affiliations & Notes
  • William K Stell
    Cell Biology & Anatomy, Hotchkiss Brain Institute, and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  • Aisha D Lillywhite
    School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada
  • Brittany J Carr
    Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • Footnotes
    Commercial Relationships   William Stell, Novartis Pharmaceuticals Incorporated (F), Novartis Pharmaceuticals Incorporated (C), Novartis Pharmaceuticals Incorporated (R); Aisha Lillywhite, None; Brittany Carr, Novartis Pharmaceuticals Incorporated (R), Novartis Pharmaceuticals Incorporated (C)
  • Footnotes
    Support   NSERC Discovery Grant (RGPIN/ 131-2013), Lions Sight Centre Fund Seed Grant, University of Calgary, and Foundation Fighting Blindness [Canada]-EYEGEYE Research Training Fund (WKS); Markin Undergraduate Student Research Program Studentship in Health and Wellness, University of Calgary (ADL); and NSERC PGS-D award (PGSD2-476058- 2015), Dr. D. Grant Gall Graduate Traineeship, Queen Elizabeth II Scholarships, and Odd Fellow Rebekah Visual Research Fund Awards (BJC)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5895. doi:
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    • Get Citation

      William K Stell, Aisha D Lillywhite, Brittany J Carr; Atropine and NO inhibit form-deprivation myopia via retinal mechanisms in the chick. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5895.

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

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Purpose : Myopia is a common refractive error, affecting increasing numbers of children worldwide. Atropine in eyedrops is used to slow myopia progression, but the site and mechanism of its action remain unknown. We have shown previously that atropine inhibits form-deprivation myopia (FDM) in chicks by activating the release of nitric oxide (NO), and that glucagon inhibits FDM by acting in retina and/or pigment epithelium. Here, we tested the hypothesis that NO inhibits FDM via glucagon, and therefore, that atropine and NO inhibit FDM by acting in the retina.

Methods : FDM was induced in 4-day (P4) White Leghorn Shaver chicks (n=10-15) by a diffuser goggle on the right eye (‘treated’: T), leaving the left eye ungoggled (‘control’: C). On days P5 & P7, we injected intravitreally 20µL of 5% ethanol-saline (vehicle), containing drug (T) or no drug (C). The drugs (concentration injected) were: glucagon (60 µM); glucagon-receptor antagonist (a-GcgR: [des-His1,Glu9]-glucagon-NH2; 60 µM); L-Arg (nitric oxide synthase [NOS] substrate; 30 mM); and NOS-inhibitor (L-NMMA; 600 µM). On P8, eyes were refracted and weighed, and external dimensions were measured. Treatment effects were expressed as the mean of the interocular differences (T-C), ±SD (refractive error: dRE; axial length: dAL), after ensuring that drug treatments did not affect the fellow control eyes. Statistics: One-way ANOVA + Tukey post-hoc; pairwise comparisons, drug vs. vehicle.

Results : FD induced myopia: dRE (-7.0 ± 2.4 D) and dAL (0.41 ± 0.27 mm). The myopic dRE was reduced significantly by glucagon (-4.1 ± 2.1 D; p<0.05) and by L-Arg (-4.8 ± 1.9 D; p<0.01); a-GcgR blocked the action of glucagon (dRE = -9.0 ± 1.9D; p<0.001), but L-NMMA did not (-5.6 ± 1.9 D; P>0.05). Differences in axial length, equatorial diameter, and wet weight were unaffected, except that L-NMMA increased dAL (0.66 ± 0.22 mm; p<0.05).

Conclusions : Inhibition of FDM by NO requires activation of glucagon receptors, which are confined to retina/RPE. Therefore, both atropine and NO inhibit FDM via sites in the retina. Glucagon changes dRE mainly by increasing choroidal thickening (Vessey et al., IOVS 2005). The increase of dAL in L-NMMA-treated eyes suggests residual release of NO during FD. Finally, since atropine prevents FDM after ablation of retinal sources of ACh (Fischer et al., Br Res 1998), atropine's acting in the retina is further evidence that it does not inhibit myopia via mAChRs.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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