Dysregulation of RPE immunosuppression during ageing: a RNA-seq study
Purpose: The ageing of the retinal pigment epithelium (RPE), and loss of subretinal immune privilege are thought to be fundamental in the development of age-related macular degeneration (AMD). This study characterised the global transcriptomic changes associated with RPE immunosuppression during ageing.
Methods: RPE-choroidal tissues were isolated from eyes of C57BL/6J mice at 3 (young) and 22 months old (aged). RNA-seq was performed on Illumina NovaSeq 6000 System using total tissue RNA. Differentially expressed genes (DEGs) analysis and functional overrepresentation analysis of DEGs were conducted via edgeR and clusterProfiler packages respectively in R.
Results: 5967 DEGs (FDR<0.05) were identified between young and aged RPE-choroid, e.g. the most dysregulated immune-modulating Orm1. Immunosuppressive DEGs Tgfb3, Thbs1, Serpinf1 and Ctla2a were significantly downregulated in ageing. 17 significantly overrepresented Gene Ontology biological processes were linked to myeloid leukocyte chemotaxis and inflammatory response (q<0.05). DEGs involved in phagocytosis and inflammatory leukocyte migration, namely Fcerlg, Itgb2 and Syk, were also recognised in previous microarray ageing studies using RPE-choroid.
Conclusions: We confirmed an age-related loss of RPE immunosuppression. With Fcerlg, Itgb2 and Syk being consistently identified across different transcriptome studies, these genes may account for recruiting subretinal phagocytic leukocytes with age, and the immune dysregulation leading to AMD.
Author: Miss Josephine Wong, The University of Melbourne
Co Author/s: Dr Alice Brandli, Dr Matt Rutar,Dr Andrew Jobling, Professor Erica Fletcher, The University of Melbourne