Geographic Atrophy in Age-Related Macular Degeneration Is Associated With Distinct T-Cell Differentiation Profile

Purpose: Increasing age is the strongest risk factor in developing AMD. Growing evidence suggests that systemic immunosenescence is implicated in its pathogenesis. This study aims to characterize age-related T-cell differentiation in late-stage AMD by comparing patients with geographic atrophy (GA) and neovascular AMD (nAMD) to a shared healthy control group. Methods: Patients with GA or nAMD were recruited from an outpatient AMD-clinic. Individuals with immunological disease, cancer or use of immune-modulating medication were excluded. Blood samples from all participants were stained with monoclonal antibodies and analyzed with flow cytometry to assess T-cell subsets (naive, central memory [CM], effector memory [EM], and effector memory with CD45ra+ [EMRA]) and expression of the age-associated costimulatory markers (CD27, CD28, and CD56). Results: One hundred twenty-eight patients were included in this study. Patients with GA demonstrated significantly higher levels of CD8+CD28-EM T cells (P = 0.038) and significantly lower levels of CD4+CD56+CM T cells (P = 0.021) compared with healthy controls. Patients with nAMD showed significantly higher levels of naive CD4+CD56+ and CD4+CD56+CM T cells (P = 0.008 and P = 0.008) compared to patients with GA. Conclusions: Patients with GA demonstrated an increased proportion of CD8+CD28- EM T cells, a finding similar to other infectious, autoimmune, and neurodegenerative disorders. The increased expression of CD56+ T cells in patients with nAMD supports CD56 having a potential role in angiogenic regulation. Contrarily, we suggest the reduced CD56 expression in patients with GA might contribute to GA pathogenesis.