Introduction: The goal of this study was to investigate the presence of ADORA2A-DRD2 heterodimers in human retinal pigment epithelial (RPE) cells; determine if 7-methylxanthine (7-MX), a nonselective adenosine receptor antagonist which was used to control myopia progression, can influence the behavior of RPE cells through the ADORA2A-DRD2 receptor pathway; and assess the changes in the expression of signaling molecules during cellular signal transduction. Methods: Human RPE cells were cultured in vitro in the presence or absence of 7-MX. Cell proliferation was evaluated with the CCK-8 assay. Apoptosis and necrosis rates were determined by annexin V–FITC/propidium iodide staining and flow cytometry. Immunofluorescence and coimmunoprecipitation were used to examine the protein expression and colocalization of ADORA2A and DRD2 in RPE cells. ADORA2A and DRD2 were knocked down with small interfering RNAs (siRNAs). Changes in the protein expression of ERK1/2 and phospho-ERK1/2 (pERK 1/2), which are signaling molecules downstream of dopamine receptors, were evaluated by Western blot analysis. Results: Immunofluorescence and coimmunoprecipitation showed that ADORA2A and DRD2 were colocalized in RPE cells. The expression of ADORA2A in RPE cells was inhibited by treatment with 50 µmol/L 7-MX for 48 h, and the expression of DRD2, ERK1/2, and pERK1/2 was increased after treatment with 50 µmol/L 7-MX for 48 h. After siRNA-mediated knockdown of DRD2 in RPE cells and further treatment with 50 µmol/L 7-MX for 48 h, the expression of DRD2 was nearly restored to the level observed in the native control. At the experimental concentrations, 7-MX and siRNAs did not affect the proliferation or apoptosis of human RPE cells. Conclusions: ADORA2A and DRD2 heterodimers were present in RPE cells. 7-MX may affect the behaviors of RPE cells through the ADORA2A-DRD2 receptor pathway. 7-MX is an inhibitor of ADORA2A receptors that can prevent inhibition of the DRD2 receptor pathway and increase DRD2 receptor pathway activity. This phenomenon may explain the mechanism of action through which 7-MX can control myopia progression.

Purpose: This study aimed to identify the key demographic, biometric, and behavioral factors that impact the treatment effect of Ortho-K in low myopia and to discover the management ideas for low myopes undergoing Ortho-K treatment. Methods: A 12-month retrospective study examined 380 individuals who received Ortho-K treatment. Stratification and multinomial logistic regression were conducted to identify biometric features and behavioral indicators associated with Ortho-K treatment outcomes in low myopes. Results: The 12-month axial length growth was significantly longer in the low myopia group than in the moderate myopia group (P<0.0001). Multivariate logistic regression analysis showed that Ortho-K only was 2.23 times more likely to have rapid axial growth than Ortho-K combined with 0.01% atropine in patients with low myopia (P=0.01; odds ratio [OR]=2.23; 95% confidence interval [CI], 1.19–4.20). Multinomial logistic regression analyses showed that in patients with low myopia, female sex (P<0.0001; OR=0.4; 95% CI, 0.22–0.72), young age (P=0.01; OR=0.79; 95% CI, 0.66–0.93), flatter K mean (P=0.004; OR=0.74; 95% CI, 0.61–0.91), and having two myopic parents (P=0.03; OR=0.18; 95% CI, 0.05–0.71) were associated with worse treatment outcomes. A diet rich in white meats, such as fish and duck (P=0.01; OR=0.06; 95% CI, 0.01–0.54), was protective behavioral factors associated with slower axial length growth in children with low myopia. Conclusions: Patients with low myopia who exhibit one or more of the demographic and biometric risk factors (young age, female, flat mean K, and two myopic parents) require heightened attention in clinic settings because of their increased risk of myopia progression. Ortho-K combined with 0.01% atropine may achieve better efficacy than Ortho-K only in low myopes. A diet rich in white meat is protective and controlled behavioral factors for these patients.