Studies on the role of the retinal dopamine/melatonin system in experimental refractive errors in chickens

Abstract

We have found that development of both deprivation-induced and lens-induced refractive errors in chickens implicates changes of the diurnal growth rhythms in the eye (Fig. 1). Because the major diurnal oscillator in the eye is expressed by the retinal dopamine/melatonin system, effects of drugs were studied that change retinal dopamine and/or serotonin levels. Vehicle-injected and drug-injected eyes treated with either translucent occluders or lenses were compared to focus on visual growth mechanisms. Retinal biogenic amine levels were measured at the end of each experiment by HPLC with electrochemical detection. For reserpine (which was most extensively studied) electroretinograms were recorded to test retinal function [Fig. 3 (C)] and catecholaminergic and serotonergic retinal neurons were observed by immunohistochemical labelling [Fig. 3(D)]. Deprivation myopia was readily altered by a single intravitreal injection of drugs that affected retinal dopamine or serotonin levels; reserpine which depleted both serotonin and dopamine stores blocked deprivation myopia very efficiently [Fig. 3(A)], whereas 5,7-dihydroxy-tryptamine (5,7-DHT), sulpiride, melatonin and Sch23390 could enhance deprivation myopia (Table 1, Fig. 5). In contrast to other procedures that were previously employed to block deprivation myopia (6-OHDA injections or continuous light) and which had no significant effect on lens-induced refractive errors, reserpine also affected lens-induced changes in eye growth. At lower doses, the effect was selective for negative lenses (Fig. 4). We found that the individual retinal dopamine levels were very variable among individuals but were correlated in both eyes of an animal; a similar variability was previously found with regard to deprivation myopia. To test a hypothesis raised by Li, Schaeffel, Kohler and Zrenner [(1992) Visual Neuroscience, 9, 483-492] that individual dopamine levels might determine the susceptibility to deprivation myopia, refractive errors were correlated with dopamine levels in occluded and untreated eyes of monocularly deprived chickens (Fig. 6). The hypothesis was rejected. Although it has been previously found that the static retinal tissue levels of dopamine are not altered by lens treatment, subtle changes in the ratio of DOPAC to dopamine were detected in the present study. The result indicates that retinal dopamine might be implicated also in lens-induced growth changes. Surprisingly, the changes were in the opposite direction for deprivation and negative lenses although both produce myopia. Currently, there is evidence that deprivation-induced and lens-induced refractive errors in chicks are produced by different mechanisms. However, findings (1), (3) and (5) suggest that there may also be common features. Although it has not yet been resolved how both mechanisms merge to produce the appropriate axial eye growth rates, we propose a scheme (Fig. 7).

Dopamine D1 Receptors Contribute Critically to the Apomorphine-Induced Inhibition of Form-Deprivation Myopia in Mice

“…3 Intravitreal injection of the D1R antagonist SCH 23390 enhanced FDM development in chickens. 49 Similarly, preliminary studies indicated the D1R agonist SKF 38393 inhibited FDM, whereas the D1R antagonist SCH 39166 enhanced FDM in mice (Zhou X, et al IOVS 2014;55:ARVO E-Abstract 3038). 30 However, other studies in chickens and tree shrews found that the development of FDM was not affected by intravitreal injection of the D1R antagonist SCH 23390.…”

Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina

“…Both D1R and D2R are implicated in refractive development. 22,23 A large body of experimental evidence supports the specific involvement of D2R in myopia development. [24][25][26] However, it is less clear whether or not D1R is involved in myopia development.…”

“…Previously identified D1R involvement is based on pharmacology studies with chicken models of myopia. 24,25,27 For example, a D1R agonist SKF38393 inhibited FDM, 28 while a D1R antagonist, SCH 23390, enhanced this response 22 and inhibited the ameliorating effects of periods of clear vision on lens-induced myopia in chicks. 29 Similarly, a D1R antagonist SCH23390 enhanced progression of naturally occurring myopia while a D1R agonist SKF38393 inhibited it in albino guinea pigs.…”

Myopia, Light and Circadian Rhythms

“…While diurnal retinal melatonin rhythms appear unaffected during form-deprivation (Hoffmann and Schaeffel 1996), the intra-vitreal injection of melatonin at relatively high doses (1000 g) increases the level of form-deprivation myopia induced in the chick (Schaeffel, Bartmann et al 1995;Hoffmann and Schaeffel 1996). Although retinal melatonin content was sampled twice a day (day and night) during monocular occlusion, and an expected diurnal variation in melatonin was found, no significant difference was found between the occluded and non-occluded eyes (Hoffmann and Schaeffel 1996).…”