In infant monkeys, high ambient lighting has dramatically different effects on the phenomena of lens-induced myopia and form-deprivation myopia.
Figure 7 illustrates the refractive errors obtained at ages corresponding to the end of the treatment period for form-deprived
17 and negative lens–reared monkeys. Data are shown for experimental groups reared under ordinary laboratory lighting and under high ambient lighting. The measurement methods, the rearing periods, and the normal and high light regimens for the previous study of ambient light effects on form-deprivation myopia
17 were virtually identical to those employed in this study.
Whereas the high lighting levels did not significantly alter the responses of infant monkeys to negative lens–induced defocus, high light levels largely prevented the development of form-deprivation myopia. At the end of the treatment period, the deprived eyes of 17 of the 18 monocularly form–deprived monkeys reared under ordinary laboratory lighting were less hyperopic/more myopic than their fellow control eyes (i.e., they consistently exhibited form-deprivation myopia). In the high light group, only two of eight form-deprived animals developed relative myopic errors in their treated eyes; in the other six high-light–reared monkeys, the deprived eyes were more hyperopic than their fellow control eyes. It is important to note that the protective effects of high light against form-deprivation myopia were maintained over a prolonged treatment period (3–4 months). In contrast, negative lens imposed defocus produced relative myopia in 11 of the 12 normal-light–reared monkeys and in all eight of the high-light–reared monkeys. These results are important because they demonstrate that high ambient lighting does not generally retard all forms of vision-induced myopia, at least not in a quantitatively similar manner. Instead the protective effects of high ambient lighting appear to be specific for or more robust for form-deprivation myopia.
The data available from chickens and tree shrews, although not conclusive, are in agreement the idea that high lighting levels affect form-deprivation myopia and lens-induced myopia in different ways. For example, over a 4 day treatment period, exposure to high lighting levels reduces the degree of form-deprivation myopia in chicks by approximately 70%. However, it is not known whether extending the treatment period by several days would eliminate the differences in deprivation myopia between normal- and high-light–reared chickens as it did in negative lens–reared animals.
16,18 Similarly, over an 11 day treatment period, elevated lighting levels significantly reduced the degree of form-deprivation myopia in tree shrews. Again, it is not known if longer treatment periods would eliminate the differences between form-deprived tree shrews reared under ordinary and high lighting levels because, as pointed out above, with longer treatment periods, two high-light–reared tree shrews fully compensated for the imposed hyperopic defocus (Siegwart JT Jr, et al.
IOVS 2012;53:ARVO E-Abstract 3457).
Although many of the anatomic changes produced by form deprivation and hyperopic defocus are similar in nature (e.g., choroidal thinning and axial elongation),
2 and many components of the visually driven signal cascade are common to both form-deprivation and lens-induced myopia (e.g., as revealed by the similar effects of muscarinic antagonists),
42 a series of experiments, primarily conducted using chickens, have demonstrated that the mechanisms responsible for form-deprivation myopia and lens-induced myopia are not identical.
2 For example, interrupting the parasympathetic inputs to the eye reduces the axial myopia produced by form deprivation,
19,43,44 but does not alter the compensating axial myopia produced by negative lens–induced hyperopic defocus.
19,45 Form deprivation produces some rapid, transient changes in retinal RNA transcript expression that are not observed with negative lens–induced defocus.
46 Serotonin antagonists reduce lens-induced myopia, but not deprivation-induced myopia.
25 And exposure to brief periods of stroboscopic lighting attenuates form-deprivation myopia much more than negative lens–induced myopia, whereas light exposure during the night preferentially attenuates lens-induced myopia, possibly reflecting differences in the roles of circadian factors in deprivation- and defocus-induced myopia.
21 In this respect, the comparisons in
Figure 7 provide clear evidence that there are also important differences in the vision-dependent mechanisms that are responsible for form-deprivation myopia and negative lens–induced myopia in primates.
Several observations indicate that the protective effects of high light against form-deprivation myopia involve the retinal dopamine system. First, form deprivation decreases the synthesis and release of retinal dopamine,
47–49 which is a strong inhibitor of axial growth. Dopamine agonists inhibit the axial elongation normally produced by form deprivation.
24,50 Dopamine antagonists block the protective effects that brief daily periods of unrestricted vision have on form-deprivation myopia.
20,51 Retinal dopamine release is enhanced by light stimulation in an intensity dependent manner.
52 and flickering lights, which also stimulate retinal dopamine release,
53 retard the axial myopia produced by form deprivation.
21 Most importantly, the protective effects of high ambient lighting on form-deprivation myopia are blocked by selective dopamine D2 antagonists.
18 These results suggest that high ambient light produces a signal that effectively stops the unregulated growth associated with the open-loop viewing conditions produced by form deprivation. In essence, in the absence of visual signals that normally regulate ocular growth (e.g., defocus) the light-stimulated release of retinal dopamine retards the development of form-deprivation myopia, possibly by reducing the intrinsic, default growth rate of the eye.
The role of retinal dopaminergic mechanisms may not be exactly the same in negative lens–induced myopia. For example, unlike form deprivation, induced hyperopic defocus does not consistently downregulate retinal dopamine levels.
22,54,55 In chickens, the nonselective dopamine agonist, apomorphine, does reduce the axial elongation produced by negative lenses,
24,56 however, in contrast to observations in form-deprived animals, D2 receptor antagonists do not prevent the protective effects of brief daily periods of unrestricted vision on lens-induced myopia.
20 Possibly the protective effects of apomorphine on lens-induced myopia are mediated via the drug's effects on serotoninergic mechanisms.
57 Regardless, the most relevant observations come from a recent parametric comparison of the effects of dopaminergic agents on deprivation-induced and lens-induced myopia in a mammalian species. Specifically, in guinea pigs with similar degrees of experimental myopia, apomorphine reduced form-deprivation myopia in a dose-dependent manner, but did not alter the course of lens-induced myopia even with dosages 100 times higher than those that completely suppressed form-deprivation myopia.
22 These observations together with the failure of high ambient lighting to alter the course of lens-induced myopia suggest that light-stimulated release of retinal dopamine may not be sufficient to block axial elongation that is driven by optical defocus (i.e., as recently suggested by Nickla and Totonelly
20 and Dong et al.,
22 the role of dopaminergic mechanisms may be different in deprivation myopia and defocus-induced myopia).