AB006. Elucidating multiple retinal mechanisms controlling mouse refractive development

Dopamine is known as a key molecule in retinal signaling pathways regulating visually guided eye growth, as evidenced by reduced retinal dopamine levels in various species when experimental myopia is generated. However, in C57BL/6 mice our recent work demonstrated that neither retinal dopamine levels, retinal tyrosine hydroxylase (rate-limiting enzyme in dopamine synthesis) levels, nor dopaminergic amacrine cell density/morphology, were altered during the development of form-deprivation myopia (FDM). These results suggest that retinal dopamine is unlikely associated with FDM development in this mouse strain. The role of dopamine in refractive development was further explored in this mouse strain when retinal dopamine levels were reduced by intravitreal injections of 6-OHDA, a neurotoxin that specifically destroys dopaminergic neurons. The dose was so chosen that retinal dopamine levels were reduced, but no significant changes in electroretinographic responses were detected. 6-OHDA induced significant myopic shifts in refraction in a dose-dependent manner, suggesting the involvement of dopamine in normal refractive development. Biometric measurements of ocular dimensions revealed that 6-OHDA resulted in a shorter axial length and a steeper cornea, while form-deprivation led to a longer axial length without changing the corneal radius of curvature. These results strongly suggest that in addition to the dopamine-independent mechanism, a dopamine-dependent mechanism works for refractive development. We have obtained evidence, suggesting that the dopamine-independent mechanism might be related to intrinsically photosensitive retinal ganglion cells (ipRGCs). Firstly, selective ablation of ipRGCs with an immunotoxin resulted in myopic shifts in refraction. Secondly, form-deprivation induced less myopic shifts in animals with ipRGC ablation.

Altered Retinal Dopamine Levels in a Melatonin-proficient Mouse Model of Form-deprivation Myopia

Reduced levels of retinal dopamine,a key regulator of eye development,are associated with experimental myopia in various species,but are not seen in the myopic eyes of C57BL/6 mice,which are deficient in melatonin,a neurohormone having extensive interactions with dopamine.Here,we examined the relationship between form-deprivation myopia(FDM)and retinal dopamine levels in melatonin-proficient CBA/CaJ mice.We found that these mice exhibited a myopic refractive shift in form-deprived eyes,which was accompanied by altered retinal dopamine levels.When melatonin receptors were pharmacologically blocked,FDM could still be induced,but its magnitude was reduced,and retinal dopamine levels were no longer altered in FDM animals,indicating that melatonin-related changes in retinal dopamine levels contribute to FDM.Thus,FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice.The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.

Effects of confined space and near vision stimulation on refractive status and vitreous chamber depth in adolescent rhesus monkeys

This study aimed to investigate the effects of sustained near vision stimulation,on the refractive development and elongation of the vitreous chamber in adolescent rhesus monkeys.A total of 12 adolescent rhesus monkeys(1.5-2.0 years old) were randomly assigned to 3 groups.In groups A(n=4) and B(n=4),monkeys were reared in close-vision cages for 8 and 4 h d-1,respectively;tiny granules were added on the cage floor to avoid visual deprivation and to encourage near gaze.In group C(n=4),monkeys were reared in open-vision cages,with non-granule food as a control.Vitreous chamber depth,refractive status,and corneal refractive power were assessed over 18 months.Paired t-test was used to compare the differences and a P-value【0.05 was considered to be statistically significant.In group A,vitreous chamber depth and optical axis elongated significantly,and refractive error shifted towards myopia during the observation period.In group B,vitreous chambers and optical axis elongated but the refractive power did not show significant changes.In group C,there was no significant elongation in vitreous chambers and optical axis,and the refractive power changed slightly towards hypermetropia.There were no significant changes in corneal refractive power in each group.Sustained near vision can promote vitreous chamber growth and induce myopic shifts in refractive power in adolescent monkeys.Our results demonstrate the potential for a primate model of near-work-related myopia.