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

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          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.

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          Most cited references114

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          Increased prevalence of myopia in the United States between 1971-1972 and 1999-2004.

          To compare US population prevalence estimates for myopia in 1971-1972 and 1999-2004. The 1971-1972 National Health and Nutrition Examination Survey provided the earliest nationally representative estimates for US myopia prevalence; myopia was diagnosed by an algorithm using either lensometry, pinhole visual acuity, and presenting visual acuity (for presenting visual acuity > or =20/40) or retinoscopy (for presenting visual acuity -2.0 diopters [D]: 17.5% vs 13.4%, respectively [P -7.9 D: 22.4% vs 11.4%, respectively [P < .001]; < or =-7.9 D: 1.6% vs 0.2%, respectively [P < .001]). When using similar methods for each period, the prevalence of myopia in the United States appears to be substantially higher in 1999-2004 than 30 years earlier. Identifying modifiable risk factors for myopia could lead to the development of cost-effective interventional strategies.
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            Homeostasis of eye growth and the question of myopia.

            As with other organs, the eye's growth is regulated by homeostatic control mechanisms. Unlike other organs, the eye relies on vision as a principal input to guide growth. In this review, we consider several implications of this visual guidance. First, we compare the regulation of eye growth to that of other organs. Second, we ask how the visual system derives signals that distinguish the blur of an eye too large from one too small. Third, we ask what cascade of chemical signals constitutes this growth control system. Finally, if the match between the length and optics of the eye is under homeostatic control, why do children so commonly develop myopia, and why does the myopia not limit itself? Long-neglected studies may provide an answer to this last question.
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              • Article: not found

              Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops.

              To compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                January 2018
                : 59
                : 1
                : 472-486
                Affiliations
                [1 ]College of Optometry, University of Houston, Houston, Texas, United States
                [2 ]Brien Holden Vision Institute, Sydney, Australia
                [3 ]Trier Research Laboratories, Hellerup, Denmark
                [4 ]Department of Optometry and Vision Science, University of New South Wales, Kensington, New South Wales, Australia
                Author notes
                Correspondence: Earl L. Smith III, University of Houston, College of Optometry, 4901 Calhoun Road, 505 J Armistead Building, Houston, TX 77204-2020, USA; esmith@ 123456uh.edu .
                Article
                iovs-58-14-65 IOVS-17-22337
                10.1167/iovs.17-22337
                5786285
                29368006
                8a2d535d-8599-4378-90fb-f581bdcafa4e
                Copyright 2018 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 1 June 2017
                : 3 December 2017
                Categories
                Anatomy and Pathology/Oncology

                myopia,hyperopia,emmetropization,7-methylxanthine,adenosine receptors

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