Oxidative Stress and Inflammation-Related mRNAs Are Elevated in Serum of a Finnish Wet Age-Related Macular Degeneration Cohort

Purpose: Localized diseases are affected by and affect the systemic environment via blood circulation. In our studies, we explored the differences in different types of circulating serum RNAs between wet age-related macular degeneration (wAMD) patients and controls. Methods: Blood samples were obtained from 60 Finnish wAMD patients and 64 controls. After serum preparation and RNA sequencing, the count data was examined for differentially expressed genes (DEGs) and further checked for enriched molecular pathways and ontology terms as well as links to clinical data. Results: In our mRNA study, we found many DEGs and some enriched pathways, including the inflammation and cell survival-associated pathway tumor necrosis factor alpha (TNFA) signaling via nuclear factor kappa-light-chain-enhancer of activated B cells (NF?B). The related DEGs were oxidized low-density lipoprotein receptor 1 (OLR1), salt inducible kinase 1 (SIK1), and coagulation factor III (F3). DEGs from degradative macular and retinal processes were also examined, many of which were also related to cardiovascular disease and maintenance. Additionally, DEG counts were inspected in relation to clinical and anti-vascular endothelial growth factor (anti-VEGF) treatment parameters, and glutamine amidotransferase-like class 1 domain-containing 3A (GATD3A) levels were found to be significantly lower in wAMD patients who had been receiving anti-VEGF treatments compared to those who had not yet received any. Conclusions: Since regulatory factors of mitochondrial function, oxidative stress, and inflammation have a significant role in the pathology of AMD, our mRNA study results may support the presence of interplay between systemic factors and wAMD development and progression. Overall design: Blood serum samples from wet age-related macular degeneration and control patients (cataract surgery patients without signs of retinal degeneration) were sequenced (one sample per patient) and total RNA counts were extracted. DESeq2 analysis was used to find differentially expressed genes / RNAs from filtered datasets, such as mRNAs, between the two patient groups as per the package documentation. In the mRNA study, an additional model with the additions of sampling age, BMI, gender, and smoking habits was also created.