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. RESULTS: AH DA levels declined across increasing AL groups and were negatively correlated with AL (r = -0.4615, p = 0.0027), but not significantly correlated with spherical equivalent. 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.