Retinal Neurotransmitter Alteration in Response to Dopamine D2 Receptor Antagonist from Myopic Guinea Pigs

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.