Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Hospital, Tianjin 300020, PR China.
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, PR China.
ACS Chem Neurosci. 2023 Sep 20;14(18):3357-3367. doi: 10.1021/acschemneuro.3c00099. Epub 2023 Aug 30.
This study aimed to investigate the changes in retinal neurotransmitters and the role of the dopamine D2 receptor (D2R) pathway in regulating the myopic refractive state. Tricolor guinea pigs were randomly divided into two groups: the normal control group (NC) and the form-deprivation myopia group (FDM). Animals in the FDM group had their right eye covered with a balloon for 4 weeks. These two groups were further divided into two subgroups based on intravitreal injection with D2R antagonist sulpiride once a week for 3 weeks (NC, NC-Sul, FDM, and FDM-Sul groups). Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to quantitatively detect the changes in 17 retinal neurotransmitters. Compared to the NC group, the concentrations of dopamine (DA) and γ-aminobutyric acid (GABA) decreased, while those of glutamate (Glu), 3-methoxytyramine (3-MT), and glycine increased, accompanied by an increase in myopic refraction and axial length (AL) in the FDM group. In the FDM-Sul group, glycine and DA levels were upregulated, whereas 3-MT and Glu levels were downregulated, accompanied by a decrease in myopic refraction and AL. The ratio of Glu to GABA (RGG) represents the balance between excitatory and inhibitory neurotransmitters. Notably, RGG changes occurred with corresponding AL changes, which increased in the FDM group and decreased in the FDM-Sul group. Decreased retinal DA concentration, with an increase in Glu, may be involved in the myopia progression. D2R antagonists might effectively slow myopia progression by increasing retinal DA, regulating Glu concentration to match GABA, and maintaining the balance between excitatory and inhibitory neurotransmitters.
本研究旨在探讨视网膜神经递质的变化以及多巴胺 D2 受体（D2R）通路在调节近视屈光状态中的作用。三色豚鼠随机分为正常对照组（NC）和形觉剥夺性近视组（FDM）。FDM 组动物右眼用气球遮盖 4 周。这两组根据每周一次玻璃体内注射 D2R 拮抗剂舒必利进一步分为两组（NC、NC-Sul、FDM 和 FDM-Sul 组），持续 3 周。采用超高效液相色谱-串联质谱法定量检测 17 种视网膜神经递质的变化。与 NC 组相比，FDM 组多巴胺（DA）和γ-氨基丁酸（GABA）浓度降低，谷氨酸（Glu）、3-甲氧基酪胺（3-MT）和甘氨酸浓度升高，近视屈光度和眼轴（AL）增加。在 FDM-Sul 组中，甘氨酸和 DA 水平上调，而 3-MT 和 Glu 水平下调，同时近视屈光度和 AL 降低。Glu 与 GABA 的比值（RGG）代表兴奋性和抑制性神经递质之间的平衡。值得注意的是，RGG 变化与相应的 AL 变化一致，即在 FDM 组中增加，在 FDM-Sul 组中减少。视网膜 DA 浓度降低，Glu 增加，可能与近视进展有关。D2R 拮抗剂通过增加视网膜 DA、调节 Glu 浓度以匹配 GABA 并维持兴奋性和抑制性神经递质之间的平衡，可能有效减缓近视进展。
