Identification of Diagnostic Biomarkers and Their Correlation with Immune Infiltration in Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the central retina, with no suitable biomarkers for early diagnosis and treatment. This study aimed to find potential diagnostic biomarker candidates for AMD and investigate their immune-related roles in this pathology. Weight gene correlation analysis was first performed based on data from the Gene Expression Omnibus database and 20 hub genes were identified. The functional enrichment analyses showed that the innate immune response, inflammatory response, and complement activation were key pathways associated with AMD. Complement C1s (C1S), adrenomedullin (ADM), and immediate early response 5 like (IER5L) were identified as the crucial genes with favorable diagnostic values for AMD by using LASSO analysis and multiple logistic regression. Furthermore, a 3-gene model was constructed and proved to be of good diagnostic and predictive performance for AMD (AUC = 0.785, 0.840, and 0.810 in training, test, and validation set, respectively). Finally, CIBERSORT was used to evaluate the infiltration of immune cells in AMD tissues. The results showed that the NK cells, CD4 memory T cell activation, and macrophage polarization may be involved in the AMD process. C1S, ADM, and IER5L were correlated with the infiltration of the above immune cells. In conclusion, our study suggests that C1S, ADM, and IER5L are promising diagnostic biomarker candidates for AMD and may regulate the infiltration of immune cells in the occurrence and progression of AMD.

Complement C1s as a diagnostic marker and therapeutic target: Progress and propective

“…It has been shown recently that the expression of C1s and another two other genes is associated with Age-related macular degeneration (AMD), a progressive neurodegenerative disease of the central retina and a leading cause of vision loss in older adults worldwide ( 98 ). Mechanistically, it is likely due to their correlation with NK cell infiltration, CD4 memory T cell activation, and macrophage polarization in AMD.…”

Innate immune biology in age-related macular degeneration

“…In a genotyping study of AMD and control patients, the NK receptor AA haplotype was, in combination with the human leukocyte antigen (HLA)-Cw*0701 allele, associated with AMD (Goverdhan et al, 2008). In another study of gene expression profiles in AMD, there was a lower prevalence of resting NK cells in AMD versus control, but the C1S, ADM, and 1ER5L genes were shown to have a positive correlation with activation of NK cells, among others, along AMD progression (Zeng et al, 2021). Further experiments in mice models have shown that in vivo depletion of interferon-γ-secreting NK cells lead to reduced choroidal neovascularization (CNV) (Lee et al, 2014).…”

“…Chemokine profiles of CD4 + and CD8 + patients differ between AMD and control conditions (Choi et al, 2022). Furthermore, in AMD versus control gene expression analysis, the AMD condition exhibited lower resting CD4 + memory T cells (Zeng et al, 2021). T cells may become activated in response to oxidative stress (Cruz-Guilloty et al, 2014).…”

Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment

“…In a more recent gene expression study, there was a lower prevalence of resting NK cells in AMD patients compared to control patients. However, the C1S, ADM and 1ER5L genes were shown to correlate positively with NK cell activation, in addition to AMD progression [ 125 ].…”