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Inhibition of experimental myopia by a dopamine agonist: Different effectiveness between form deprivation and hyperopic defocus in guinea pigs

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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.
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... Among the signals, the dopaminergic signaling is the most characterized. 18,[34][35][36]41,43,44,[92][93][94][95][96][97][98] DA is considered as a stop signal in most species and myopia induction protocols. 18,36,41,43,44,50,93,94,97,99,100 Our data revealed that retinal levels of both DA and DOPAC in Lrit3 −/− eyes were halved compared to controls eyes (Fig. 1). ...
... 18,[34][35][36]41,43,44,[92][93][94][95][96][97][98] DA is considered as a stop signal in most species and myopia induction protocols. 18,36,41,43,44,50,93,94,97,99,100 Our data revealed that retinal levels of both DA and DOPAC in Lrit3 −/− eyes were halved compared to controls eyes (Fig. 1). In the retina, DA is synthesized and released by dopaminergic amacrines cells. ...
... 3,4 Dopamine (DA) is an important neurotransmitter in the retina, mediating retinal development, visual signaling, and refractive development. 21 It is proven to be a "stop" signal for myopia, [22][23][24][25][26] although the exact mechanism remains unclear. DACs, which synthesize and release DA in the retina, are important inhibitory interneurons that affect nearly all retinal cells and visual pathways. ...
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It has been shown that visual deprivation leads to a myopic refractive error and also reduces the retinal concentration of dopamine. Exogenously 3,4-dihydroxy-L-phenylalanine (levodopa, L-DOPA) can be converted into dopamine in vivo, which safely and effectively treats Parkinson disease. Moreover, L-DOPA was also used in the treatment of amblyopia in clinical studies. However, the effect of L-DOPA on the development of myopia has not been studied. The aim of this study was to investigate whether intraperitoneal injection of L-DOPA could inhibit form-deprivation myopia in guinea pigs and to explore a new strategy for drug treatment of myopia. Sixty guinea pigs, at age of 4 weeks, were randomly divided into six groups: normal control, L-DOPA group, saline group, deprived group, deprived plus L-DOPA group, and deprived plus saline group. Form deprivation was induced with translucent eye shields on the right eye and lasted for 10 days. L-DOPA was injected intraperitoneally into the guinea pig once a day. The corneal radius of curvature, refraction, and axial length were measured in all animals. Subsequently, retinal dopamine content was evaluated by high-performance liquid chromatography with electrochemical detection. Ten days of eye occlusion caused the form-deprived eyes to elongate and become myopic, and retinal dopamine content to decrease, but the corneal radius of curvature was not affected. Repeated intraperitoneal injection of L-DOPA could inhibit the myopic shift (from -3.62 +/- 0.98 D to -1.50 +/- 0.38 D; p < 0.001) due to goggles occluding and compensate retinal dopamine (from 0.65 +/- 0.10 ng to 1.33 +/- 0.23 ng; p < 0.001). Administration of L-DOPA to the unoccluded animals had no effect on its ocular refraction. There was no effect of intraperitoneal saline on the ocular refractive state and retinal dopamine. Systemic L-DOPA was partly effective in this guinea pig model and, therefore, is worth testing for effectiveness in progressing human myopes.