Correlation of Aqueous Humor Dopamine with Axial Length and Its Regulation by TGFβ2 in Myopia

PURPOSE: To examine whether intraocular dopamine is associated with axial length in human high myopia and to investigate whether transforming growth factor beta 2 (TGFβ2) regulates dopamine D5 receptor (DRD5)-linked inflammatory signaling in retinal pigment epithelium (RPE). METHODS: Aqueous humor (AH) dopamine (DA) levels were measured by high-performance liquid chromatography in the right eyes of 40 patients with high myopia and analyzed in relation to axial length (AL). In a 28-day form-deprivation myopia (FDM) guinea pig model, RPE DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, DRD5 and TGFβ2 expression, and inflammatory cytokines were assessed. ARPE-19 cells were treated with TGFβ2 with or without fenoldopam, and DRD5 was further silenced by small interfering RNA (siRNA) to evaluate DRD5 dependence. FDM eyes showed axial elongation, myopic refractive shift, reduced RPE DA and DOPAC levels, decreased DRD5 expression, increased TGFβ2 expression, and elevated IL-6 and TNF-α levels. In ARPE-19 cells, TGFβ2 suppressed DRD5 expression and activated nuclear factor kappa B (NF-κB)-associated inflammatory responses, whereas fenoldopam restored DRD5 expression and reduced IL-6, TNF-α, and p-p65/p65 levels. DRD5 knockdown weakened the anti-inflammatory effect of fenoldopam. CONCLUSION: Lower AH DA is associated with longer AL in high-myopia eyes. The animal and cell data support a TGFβ2-DRD5-NF-κB axis in RPE inflammatory activation, suggesting that impaired dopaminergic signaling may contribute to myopia-associated axial elongation.