Retinal levels of DA and DOPAC have been determined by HPLC in normal C57BL/6 mice. In a study concerning circadian rhythms of DA in mouse retina, Doyle et al.
54 reported that retinal DA and DOPAC concentrations in C57BL/6 mice fluctuate within the range of 1000 to 1200 pg/retina and 100 to 200 pg/retina, respectively across different times of the day. In another study, these values measured at ZT 3 to 4 are 545.33 ± 14.50 pg/retina (DA) and 187.3 ± 10.67 pg/retina (DOPAC).
76 The data reported in this work for normal eyes (daytime DA: 0.260 ± 0.011 ng/mg, which equals to 771 ± 21.5 pg/retina; nighttime DA: 0.310 ± 0.064 ng/mg, which equals to 700 ± 12.5 pg/retina; daytime DOPAC: 0.046 ± 0.003 ng/mg, which equals to 137 ± 8 pg/retina; nighttime DOPAC: 0.028 ng/mg, which equals to 61.9 ± 11.7 pg/retina) are quite close to these data, with a similar order of variations. No data concerning mouse vitreal DOPAC levels are available, but our results (daytime: 0.070 ± 0.005 ng/μL, which equals to 455.407 ± 50.704 nM; nighttime: 0.022 ± 0.001 ng/μL, which equals to 128.217 ± 7.230 nM) were comparable with those obtained in chicks (approximately 0.019 ± 0.006 ng/μl
77) and frogs (approximately 311 ± 29 nM
78). Furthermore, the expression of DAT in the retina was also unchanged, suggesting no changes in extracellular retinal DA concentrations in myopic eyes. There are multiple lines of evidence in favor of the assumption that DAT expression level responds to the level of extracellular DA. Dopamine transporter is known to be the major mechanism for removal of extracellular DA in mammalian brain
79,80 and genetic deletion of DAT leads to 100 times longer dopamine persistence in the extracellular space.
79,81 More importantly, retinal DAT expression is altered in several FDM models that show reduced retinal DA levels.
73,74 All these results suggest that the development of FDM is not related to retinal DA levels in this mouse strain. The notion that retinal levels of DA and DOPAC are unaltered is further strengthened by the intactness of the retinal DA synthesis system in this myopic model, as evidenced by no significant changes in TH expression at protein or mRNA levels, densities of TH
+ amacrine cells, and areas occupied by processes of these cells. In this context we have noticed that in mice lacking the nyctalopin gene (
nob mice), thus leading to a loss of the ON functional pathway and showing markedly lower levels of retinal DA and DOPAC, no significant myopic shift was found in normal visual environment (without form deprivation), even though these mice showed an increased susceptibility to FDM.
76 Moreover, these mice are more hyperopic than the wild-type C57BL/6 mice.
76 If reduced levels of DA and DOPAC were directly related to the development of myopia, they should have been myopic in normal visual environment. In other words, these results do suggest that the retinal DA levels may not be a key factor leading to the development of myopia in the
nob mouse. Needless to say, extreme caution should be taken for interpreting any data obtained in this strain, given its unexpected behavior and possible developmental reorganization caused by mutation.
82–84 It must also be emphasized that the unchanged retinal levels of DA and the intactness of the DA system in this mouse myopic model should not be considered to oppose to the hypothesis that DA plays an essential role in the development of myopia, which has been proposed based on results obtained in other species. Any conclusion drawn from this work should thereby be restricted to the C57BL/6 mouse at this stage and could be expanded to other species only when further experimental evidence is provided. The unchanged retinal DA levels and the intactness of the DA system also do not necessarily imply that DA plays no role in myopia development of this mouse strain. A speculation is that, instead of DA levels, DA receptor levels (the expression levels of DA receptors) may be somehow be associated with myopic development. Recently, there are some preliminary studies suggesting that genetic and pharmacological manipulation of dopamine D
2 receptors in mice could influence the eye refraction and the development of FDM.
85 More solid evidence must be provided for strengthening such possibility.