Serum endothelin 1 and interleukin 8 are elevated in patients with active wet age‐related macular degeneration without a clear serological link to epithelial‐mesenchymal transition: a Finnish cohort

Purpose

To see if patients with wet age-related macular degeneration (wAMD) have significant changes in their systemic levels of epithelial-mesenchymal transition (EMT)-related serum markers.

Methods

We compared 71 Finnish wAMD patients undergoing anti-VEGF-A (vascular endothelial growth factor A) treatments to 64 age-adjusted controls. The serum levels of EGF (epidermal growth factor), ET-1 (endothelin 1), IL-8 (interleukin 8), TGF-β1 (transforming growth factor beta 1), and VEGF-A were measured using enzyme-linked immunosorbent assays.

Results

Significant differences between the groups were found in BMI (p < 0.001), as well as blood pressure and anti-coagulation medication usage (p = 0.001 and p = 0.007, respectively), all of which were higher for the wAMD patients. The median levels of ET-1 (p = 0.003), IL-8 (p < 0.001), and VEGF-A (p = 0.050) were also statistically different. Higher levels of ET-1 and IL-8 and lower levels of VEGF-A were found in the wAMD patients, with anti-VEGF-A treatments explaining the lower levels of VEGF-A. In a crude binomial logistic regression model, ET-1 (p = 0.041), IL-8 (p = 0.024), and free active TGF-β1 (p = 0.038) were found to associate with wAMD, while falling out of significance in an adjusted model with patient characteristics included. Additionally, ET-1 was found to be associated with the use of various cardiovascular disease (CVD) medications.

Conclusions

No conclusive evidence was found that wAMD-related EMT would cause significant changes in the systemic serum marker levels. This could, in part, be explained by the fact that wAMD patients naturally exhibit individual types of wAMD characteristics, shown by them requiring different kinds and amounts of medications. ET-1 and IL-8 are more easily related to CVD and general inflammation than EMT, but it must be kept in mind that systemic level imbalances in these and other signalling molecules may predispose patients to develop wAMD and progress to its more severe forms.

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