Epithelial–mesenchymal transition‐related serum markers ET‐1, IL‐8 and TGF‐β2 are elevated in a Finnish wet age‐related macular degeneration cohort

Abstract

It has been hypothesized that epithelial-mesenchymal transition (EMT) may occur in the retinal pigment epithelium of advanced stage age-related macular degeneration (AMD). Various serum and plasma growth factors and inflammatory mediators have been linked to AMD. We were interested in finding out whether systemic levels of EMT-associated markers were altered in the serum of wet AMD patients. Serum biomarkers associated with the various pathological processes of AMD may present an avenue towards identifying and characterizing the birth mechanisms of wet AMD, its progression and severity, paving the way towards the application of precision medicine. Methods:We chose to measure the serum levels of known biomarkers of EMT -EGF (epidermal growth factor), ET-1 (endothelin 1), IL-8 (interleukin 8), TGF-b1 and TGF-b2 (transforming growth factor-beta 1 and 2) and VEGF-A (vascular endothelial growth factor A)using enzyme-linked immunosorbent assays. We measured them from 71 Finnish wet AMD patients who were receiving intravitreal anti-VEGF-A injection treatments, as well as 64 age-adjusted controls. Results:We found significantly elevated levels of ET-1, IL-8 and TGF-b2 in the serums of wet AMD patients.Conclusions: ET-1, IL-8 and TGF-b2 appear to be useful serum biomarkers in understanding active wet AMD. However, we cannot conclude that local retinal EMTprocesses could be observed from the corresponding systemic serum biomarkers in patients undergoing anti-VEGF-A treatments.

VEGFA Haplotype and VEGF-A and VEGF-R2 Protein Associations with Exudative Age-Related Macular Degeneration

“…VEGF-A serum levels, as well as VEGFA SNPs, are widely studied in AMD patients. While we did not find any statistical differences in VEGF-A serum levels between the exudative AMD patients and controls, we confirmed results from several other studies which included total AMD patients or only exudative AMD patients, consisting of 27 to 71 samples per group in different populations [53][54][55][56][57][58][59][60]. Further studies revealed significantly elevated VEGF-A levels in exudative AMD patients compared to controls [61,62].…”

A Linkage between Angiogenesis and Inflammation in Neovascular Age-Related Macular Degeneration

“…Many proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, IL-6, IL-1β, IL-8 and VEGF, have both angiogenic and proinflammatory activity [ 14 , 105 , 106 , 107 , 108 ]. All the previously mentioned cytokines have been also linked to development of AMD [ 14 , 105 , 109 , 110 , 111 , 112 , 113 ]. Upregulation of these factors activates the endothelial cells and promotes angiogenesis ( Figure 4 ).…”

Inflammasome activation in response to aberrations of cellular homeostasis in epithelial cells from human cornea and retina

“…IL‐8 is a neutrophil‐recruiting chemokine that also induces angiogenesis and the generation of superoxide radicals (Matsushima et al., 2022). Interestingly, the levels of IL‐8 have been found to be increased in the serum samples obtained from wet AMD patients when compared to their age‐matched controls (Liukkonen et al., 2022). In agreement with these proposals, the present study highlights the role of IL‐8 in the pathogenesis of AMD.…”