The Adenosine Receptor Antagonist, 7-Methylxanthine, Alters Emmetropizing Responses in Infant Macaques.

Abstract

Purpose:

Previous studies suggest that the adenosine receptor antagonist, 7-methylxanthine (7-MX), retards myopia progression. Our aim was to determine whether 7-MX alters the compensating refractive changes produced by defocus in rhesus monkeys.

Methods:

Starting at age 3 weeks, monkeys were reared with -3 diopter (D; n = 10; 7-MX -3D/pl) or +3D (n = 6; 7-MX +3D/pl) spectacles over their treated eyes and zero-powered lenses over their fellow eyes. In addition, they were given 100 mg/kg of 7-MX orally twice daily throughout the lens-rearing period (age 147 ± 4 days). Comparison data were obtained from lens-reared controls (-3D/pl, n = 17; +3D/pl, n = 9) and normal monkeys (n = 37) maintained on a standard diet. Refractive status, corneal power, and axial dimensions were assessed biweekly.

Results:

The -3D/pl and +3D/pl lens-reared controls developed compensating myopic (-2.10 ± 1.07 D) and hyperopic anisometropias (+1.86 ± 0.54 D), respectively. While the 7-MX +3D/pl monkeys developed hyperopic anisometropias (+1.79 ± 1.11 D) that were similar to those observed in +3D/pl controls, the 7-MX -3D/pl animals did not consistently exhibit compensating myopia in their treated eyes and were on average isometropic (+0.35 ± 1.96 D). The median refractive errors for both eyes of the 7-MX -3D/pl (+5.47 D and +4.38 D) and 7-MX +3D/pl (+5.28 and +3.84 D) monkeys were significantly more hyperopic than that for normal monkeys (+2.47 D). These 7-MX-induced hyperopic ametropias were associated with shorter vitreous chambers and thicker choroids.

Conclusions:

In primates, 7-MX reduced the axial myopia produced by hyperopic defocus, augmented hyperopic shifts in response to myopic defocus, and induced hyperopia in control eyes. The results suggest that 7-MX has therapeutic potential in efforts to slow myopia progression.

• Authors: Li-Fang Hung, Baskar Arumugam, Lisa Ostrin, Nimesh Patel, Klaus Trier, Monica Jong, Earl L Smith III
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 59 Issue 1 Pg. 472-486 (01 01 2018) ISSN: 1552-5783 [Electronic] United States
• PMID: 29368006 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Purinergic P1 Receptor Antagonists
• Xanthines
• 7-methylxanthine

Topics

• Administration, Oral
• Animals
• Animals, Newborn
• Anisometropia (drug therapy, physiopathology)
• Biometry
• Disease Models, Animal
• Emmetropia (drug effects, physiology)
• Hyperopia (physiopathology)
• Macaca mulatta
• Myopia (drug therapy, physiopathology)
• Purinergic P1 Receptor Antagonists (administration & dosage, therapeutic use)
• Xanthines (administration & dosage, therapeutic use)