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Li-Fang Hung, Baskar Arumugam, Lisa A Ostrin, Klaus Trier, Monica Jong, Earl L Smith; The Effects of Adenosine Antagonist, 7-Methylxanthine, on Emmetropization in Rhesus Monkeys. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5462.
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© ARVO (1962-2015); The Authors (2016-present)
Laboratory studies and clinical trials suggest that the adenosine receptor antagonist, 7-methylxanthine (7MX), retards myopia progression. The aim of this study was to determine whether 7MX alters the compensating refractive changes produced by optical defocus in rhesus monkeys.
Starting at age 3 weeks, monkeys (n=37) were reared with either -3D (n=24) or +3D (n=13) lenses over their treated eyes and plano lenses over their fellow eyes. Ten and 6 of the monkeys reared with -3D (-3-7MX) and +3D lenses (+3-7MX) were also given 100 mg/kg of 7MX by mouth BID until the end of lens wear (143±15 days old). The eye’s refractive status, corneal power and axial dimensions were assessed periodically throughout the treatment period. Data on normal refractive development were obtained from 35 untreated monkeys.
At the end of the treatment period, the control animals reared with monocular +3 and -3 D lenses exhibited significant compensating hyperopic (+1.72±0.56D) and myopic anisometropias (-2.13±1.18D), respectively. In contrast the -3-7MX monkeys exhibited significant hyperopic ametropias in both eyes (median: treated eye, +5.47D, p=0.002; fellow eye, +4.28D, p=0.01), but were on average isometropic (+0.34±1.96 D). During the treatment period, the +3-7MX monkeys also manifest significant hyperopic shifts in both eyes, which were larger than those observed in +3 D controls (treated eyes: 2.32±1.06D vs 0.03±0.64D, p=0.002; fellow eyes: 0.66±1.13D vs -1.74±0.68D, p=0.003), but interestingly similar amounts of hyperopic anisometropia (+1.72±0.56D). The relative hyperopic changes in the 7MX-treated monkeys were associated with increases in choroidal thickness and reduced vitreous chamber elongation rates.
The results demonstrate that, in primates, daily systemic administration of 7-MX increases choroidal thickness, reduces overall axial elongation rates, promotes the development of hyperopia in control eyes, blocks compensating myopia produced by hyperopic defocus, and augments hyperopic shifts in response to imposed myopic defocus. The results suggest that adenosine receptors play a critical role in emmetropizing responses, especially to hyperopic defocus.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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