Autophagy and inflammation related RNA levels are elevated in Finnish age‐related macular degeneration patient blood serum

Abstract

AbstractPurpose: Patients with wet age‐related macular degeneration (wAMD) exhibit altered levels of genetic and epigenetic material in their systemic circulation. Cellular level processes related to autophagy and inflammation have previously been shown to associate with wAMD and its progression. Thus, measuring RNA levels in peripheral blood may help understand the causes of wAMD, explain why there exist differences in patient response to treatments, and find genetic commonalities between other diseases and wAMD.Methods: Blood samples as well as patient characteristics were collected from 63 wAMD patients and 65 controls. Serum was separated and Illumina Stranded Total RNA library preparation kits were used for RNA‐sequencing. Data was processed and analysed for differentially expressed (DE) genes in R using the edgeR package.Results: Preliminary results show that, among others, microtubule associated protein 1 light chain 3 beta 2 (MAP1LC3B2) levels are significantly elevated (p = 0.028, logFC = 1.631) in Finnish wAMD patients compared to the control group. Higher levels of ankyrin 3 (ANK3) and cluster of differentiation 96 (CD96) were found in the control group (p = 0.001, logFC = −1.805; p = 0.002, logFC = −1.725). In addition, MAP1LC3B2 levels were elevated in patients with blood pressure medication (p = 0.025, logFC = 1.943).Conclusions: LC3B2, produced by MAP1LC3B2, is a member of LC3 protein family involved in autophagosomal vacuole formation and mitophagy. Significant changes in the expression of LC3 family members can be a sign of issues in the autophagic process. Ankyrin‐3 is part of the cytoskeleton structure and takes part in vesicle‐mediated transport. Ankyrins have been found to have notable interactions with the LC3 family. CD96 promotes immune cell adhesion during late‐stage immune response, helping movement in inflamed areas. Though we have found several DE genes, further analysis is needed to better understand these differences and their interplay with the various patient characteristics.