Acupuncture modulates myopia development by activating dopamine – dopamine receptor 1 signaling pathway and lowering NLRP3 inflammasome activation
Background: Dopamine is known to act as a stop signal for eye growth and affects the development of myopia. Acupuncture has been widely used to treat myopia clinically which slows its progression. The goal of this study was to investigate the mechanisms by which acupuncture ameliorated myopia development by the dopamine mediated inflammasome inhibition.
Methods: A form-deprivation myopia animal model in Syrian hamsters was used. Acupuncture was applied on Hegu (LI4) and Taiyang (EX-HN5) acupoints every other day for 21 days. The levels of dopamine, phosphor-tyrosine hydroxylase, dopamine transporter, dopamine receptor 1 and 2 (D1R, D2R) were determined by immunofluorescence staining or mass spectrometry. We also determined the levels of nuclear factor κB (NFκB), tumor necrosis factor α, interleukin 1β and 6 and NLR family pyrin domain containing 3 (NLRP3) by immunofluorescence, immunohistochemistry staining and western blot. The dopamine agonist, apomorphine, was also used to evaluate the inflammasome inhibiting activities in primary retinal pigment epithelial cells. A D1R inhibitor, SCH39166 was also administered in hamsters.
Results: Our results indicated that acupuncture inhibit myopia development with increasing the level of dopamine in the retina. The expression level of tyrosine hydroxylase and dopamine transporter were also increase in acupuncture treated eyes compared to control and sham control eyes. Moreover, we also found an increase in the expression levels of D1R while decrease the level of D2R. The level of cyclic AMP, a second messenger induced by the dopamine – D1R signaling pathway was also elevated. The levels of inflammation related transcription factor nuclear factor κB (NFκB), cytokines such as TNFα, IL6 and IL1β were lowered by acupuncture treatment compared to control and sham control groups. The activation of inflammasome was also inhibited by acupuncture. The importance of the dopamine – D1R signaling pathway was also confirmed by applying the D1R inhibitor, SCH39166. SCH39166 prohibited the protective effect of acupuncture on myopia development.
Conclusion: Our findings suggested that acupuncture inhibited myopia development through suppressing inflammation which was initiated by activating the dopamine – D1R signaling pathway.