Recovery from Form-Deprivation Myopia in Rhesus Monkeys

College of Optometry, University of Houston, Houston, Texas 77204-2020, USA.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.4). 11/2004; 45(10):3361-72. DOI: 10.1167/iovs.04-0080
Source: PubMed


Although many aspects of vision-dependent eye growth are qualitatively similar in many species, the failure to observe recovery from form-deprivation myopia (FDM) in higher primates represents a significant potential departure. The purpose of this investigation was to re-examine the ability of rhesus monkeys (Macaca mulatta) to recover from FDM.
Monocular form deprivation was produced either with diffuser spectacle lenses (n = 30) or by surgical eyelid closure (n = 14). The diffuser-rearing strategies were initiated at 24 +/- 3 days of age and continued for an average of 115 +/- 20 days. Surgical eyelid closure was initiated between 33 and 761 days of age and maintained for14 to 689 days. After the period of form deprivation, the animals were allowed unrestricted vision. The ability of the animals to recover from treatment-induced refractive errors was assessed periodically by retinoscopy, keratometry, and A-scan ultrasonography. Control data were obtained from 35 normal monkeys.
At the onset of unrestricted vision, the deprived eyes of 18 of the diffuser-reared monkeys and 12 of the lid-sutured monkeys were at least 1.0 D less hyperopic or more myopic than their fellow eyes. The mean (diffuser = -4.06 D, lid-suture = -4.50 D) and range (diffuser = -1.0 to -10.19 D, lid-suture = -1.0 to -10.25 D) of myopic anisometropia were comparable in both treatment groups. All 18 of these diffuser-reared monkeys demonstrated recovery, with 12 animals exhibiting complete recovery. The rate of recovery, which was mediated primarily by alterations in vitreous chamber growth rate, declined with age. None of the lid-sutured monkeys exhibited clear evidence of recovery. Instead, 8 of the 12 lid-sutured monkeys exhibited progression of myopia.
Like many other species, young monkeys are capable of recovering from FDM. However, the potential for recovery appears to depend on when unrestricted vision is restored, the severity of the deprivation-induced axial elongation, and possibly the method used to produce FDM.

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Available from: Chea-Su Kee, Mar 25, 2014
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    • "Guinea pigs are a promising alternative to chickens and other mammals for the study of experimental myopia [34,53-56]. They develop myopia more rapidly compared to monkeys [57-59] and have shown that local DA signaling plays a significant role in inhibition of form deprivation myopia [5,6,60]. "
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    ABSTRACT: The dopamine (DA) system in the retina is critical to normal visual development as lack of retinal DA signaling may contribute to myopic development. The involvement of DA in myopic development is complex and may be different between form deprivation and hyperopic defocus. This study evaluated effects of a non-selective DA receptor agonist, apomorphine (APO) on refractive development in guinea pigs treated with form deprivation or hyperopic defocus. APO was subconjunctivally injected daily for 11 days in form-deprived (0.025 to 2.5 ng/µl) and defocused (0.025 to 250 ng/µl) eyes. Changes in ocular biometry and retinal concentration of DA and its metabolites (DOPAC) were measured in the 2 animal models to assess the level of DA involvement in each of the models (the less the change, the lower the involvement). Similar myopic degree was induced in both the deprived and defocused eyes (-4.06 D versus -3.64 D) at 11 days of the experiment. DA and DOPAC levels were reduced in the deprived eyes but did not change significantly in the defocused eyes compared to the fellow and normal control eyes. A subconjunctival injection of APO daily for 11 days at concentrations ranged from 0.025 to 2.5 ng/µl inhibited form deprivation myopia in a concentration-dependent manner. By contrast, the APO treatment ranged from 0.025 to 250 ng/µl did not effectively inhibit the defocus-induced myopia and the associated axial elongation. DA signaling may play a more critical role in form deprivation myopia than in defocus-induced myopia, raising a question whether the mechanisms of DA signaling are different under these two types of experimental myopia.
    Molecular vision 10/2011; 17:2824-34. · 1.99 Impact Factor
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    • "In placental mammals and primates, the rate of vitreous chamber elongation is inversely related to the rate of proteoglycan synthesis in the posterior sclera (McBrien et al., 2000; Moring et al., 2007; Norton and Rada, 1995; Rada et al., 2000; Troilo et al., 2006) while in the chick, increased axial elongation and development of myopia are associated with significant increases in proteoglycan synthesis in the cartilaginous layer of the sclera (Christensen and Wallman, 1991; Gentle et al., 2001; Marzani and Wallman, 1997; McBrien et al., 1991; Rada et al., 1991, 1994). In both chicks and primates, visually induced changes in ocular elongation and sclera proteoglycan synthesis are reversible; restoration of unrestricted vision (and the resultant myopia) results in a temporary cessation of axial growth, eventually leading to re-establishment of emmetropia ( " recovery " ) in the formerly deprived eye (McBrien et al., 2000; Siegwart and Norton, 1998; Qiao-Grider, et al., 2004; Rada et al., 1992; Wallman and Adams, 1987). Moreover, the ocular response to FD or defocus is rapid, leading to detectible changes in vitreous chamber depth within hours (Winawer and Wallman, 2005). "
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    ABSTRACT: During the recovery from form deprivation myopia (myopic defocus), the rate of proteoglycan synthesis in the posterior sclera decreases co-incident with a deceleration of axial elongation. The choroid has been implicated in the regulation of scleral proteoglycan synthesis, possibly through the synthesis and secretion of scleral growth inhibitors. Therefore these studies were carried out to attempt to establish a causal relationship between choroidal secretion and the inhibition of scleral proteoglycan synthesis during the recovery from induced myopia. Chicks were form vision deprived for 10 days followed by a recovery period (3 h-20 days) of unrestricted vision. Sclera and choroids (5 mm punches) were isolated from control and treated eyes. The rate of proteoglycan synthesis was estimated by the incorporation of (3)(5)c in cetylpyridinium chloride-precipitable glycosaminoglycans by isolated sclera of control and treated eyes. Additionally, choroids from control and treated eyes were placed in co-culture with untreated age-matched normal chick sclera for 20-24 h, after which time sclera were removed and scleral proteoglycan synthesis rates were determined. Following removal of occluders, a biphasic decline was observed in scleral proteoglycan synthesis: A rapid decline in proteoglycan synthesis (-7.6% per hr; r(2) = 0.923) was observed over the first 12 h of recovery, followed by a slow decline extending from 12 to 96 h (-0.3% per hr; r(2) = 0.735). Proteoglycan synthesis rates gradually increased to control levels over the next 96 h at a rate of +0.3% per hr. No relative proteoglycan inhibition was observed when untreated sclera were co-cultured with choroids from eyes recovering for 0-4 days, whereas co-culture of untreated sclera with choroids from eyes recovering for 5 and 8 days resulted in significant inhibition of sclera proteoglycan synthesis, relative to that of sclera co-cultured with choroids from control eyes (≈-24%, P < 0.05, paired t-test). In conclusion, recovery from induced myopia is characterized by a rapid decline in proteoglycan synthesis which occurs within the first 12 h of unrestricted vision as a well as a slower more gradual decline that occurs over the next four days. Choroidal inhibition of scleral proteoglycan synthesis in vitro occurs during the second phase of decline and is most likely related to increased choroidal permeability; whereas the rapid decline in proteoglycan synthesis that occurs during the first 12 h of recovery is regulated by an independent, yet to be identified mechanism.
    Experimental Eye Research 02/2011; 92(5):394-400. DOI:10.1016/j.exer.2011.02.011 · 2.71 Impact Factor
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    • "These eyes generally respond to the myopic refractive state by reducing their growth rate while the eye's optics continue to mature, so that they recover from the induced myopia (Wallman and Adams, 1987; Qiao-Grider et al., 2004; Troilo and Nickla, 2005; Howlett and McFadden, 2006; Norton et al., 2010). In chicks, monkeys, and tree shrews, recovery is more rapid and consistent in young animals compared to older animals (Wallman and Adams, 1987; Siegwart, Jr. and Norton, 1998; Qiao-Grider et al., 2004; Norton et al., 2010) suggesting that the emmetropization mechanism may become less effective at using myopia to guide recovery in older animals. It is not known if this reduced effectiveness is due to sensory (retinal) changes or to changes in the ability to use myopic refractive error information to slow axial elongation. "
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    ABSTRACT: We examined normal emmetropization and the refractive responses to binocular plus or minus lenses in young (late infantile) and juvenile tree shrews. In addition, recovery from lens-induced myopia was compared with the response to a similar amount of myopia produced with plus lenses in age-matched juvenile animals. Normal emmetropization was examined with daily noncycloplegic autorefractor measures from 11 days after natural eye-opening (days of visual experience [VE]) when the eyes were in the infantile, rapid growth phase and their refractions were substantially hyperopic, to 35 days of VE when the eyes had entered the juvenile, slower growth phase and the refractions were near emmetropia. Starting at 11 days of VE, two groups of young tree shrews wore binocular +4 D lenses (n=6) or -5 D lenses (n=5). Starting at 24 days of VE, four groups of juvenile tree shrews (n=5 each) wore binocular +3 D, +5 D, -3 D, or -5 D lenses. Non-cycloplegic measures of refractive state were made frequently while the animals wore the assigned lenses. The refractive response of the juvenile plus-lens wearing animals was compared with the refractive recovery of an age-matched group of animals (n=5) that were myopic after wearing a -5 D lens from 11 to 24 days of VE. In normal tree shrews, refractions (corrected for the small eye artifact) declined rapidly from (mean±SEM) 6.6±0.6 D of hyperopia at 11 VE to 1.4±0.2 D at 24 VE and 0.8±0.4 D at 35 VE. Plus 4 D lens treatment applied at 11 days of VE initially corrected or over-corrected the young animals' hyperopia and produced a compensatory response in most animals; the eyes became nearly emmetropic while wearing the +4 D lenses. In contrast, plus-lens treatment starting at 24 days of VE initially made the juvenile eyes myopic (over-correction) and, on average, was less effective. The response ranged from no change in refractive state (eye continued to experience myopia) to full compensation (emmetropic with the lens in place). Minus-lens wear in both the young and juvenile groups, which initially made eyes more hyperopic, consistently produced compensation to the minus lens so that eyes reached age-appropriate refractions while wearing the lenses. When the minus lenses were removed, the eyes recovered quickly to age-matched normal values. The consistent recovery response from myopia in juvenile eyes after minus-lens compensation, compared with the highly variable response to plus lens wear in age-matched juvenile animals suggests that eyes retain the ability to detect the myopic refractive state, but there is an age-related decrease in the ability of normal eyes to use myopia to slow their elongation rate below normal. If juvenile human eyes, compared with infants, have a similar difficulty in using myopia to slow axial elongation, this may contribute to myopia development, especially in eyes with a genetic pre-disposition to elongate.
    Experimental Eye Research 11/2010; 91(5):660-9. DOI:10.1016/j.exer.2010.08.010 · 2.71 Impact Factor
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