Impaired Vagal Tone Function-Based Regulation of Systemic Inflammation in Patients With Neovascular Age-Related Macular Degeneration

PURPOSE: The purpose of this study was to investigate vagal nerve function and correlation to CD4+ T-cell population in patients with neovascular age-related macular degeneration (nvAMD) and healthy individuals.

METHODS: This study is a prospective case-control study including 36 patients with nvAMD and 40 healthy individuals. We measured the proxy of vagus nerve activity, the resting heart rate variability (HRV). Freshly sampled venous blood was prepared to measure CD4+ T-cell populations regulated by the vagal tone (regulatory T cells [Tregs], recently thymic emigrant Tregs, naïve Tregs, and effector memory T cells).

RESULTS: Compared with healthy individuals, patients with nvAMD had significantly lower HRV (low frequency/high frequency [LF/HR] ratio, P = 0.037 and standard deviation [SD] ratio, P = 0.011), indicating impaired vagal function. HRV measures negatively correlated to the proportion of Tregs (square root of the mean squared difference of successive NN intervals [RMSSD], P = 0.046) and memory T cells (RMSSD, P = 0.046) in healthy individuals, suggesting an intact regulatory capacity. These correlations were not found in patients with neovascular AMD, suggesting an impaired vagus nerve-regulatory T cell axis. Patients with nvAMD had significantly higher Tregs (P = 0.0005), naïve Tregs (P = 0.016), and recent thymic emigrant Tregs (P = 0.015).

CONCLUSIONS: Vagal tone is impaired in patients with nvAMD which disharmonizes with increased Tregs in the systemic circulation. These altered regulators may be the key to increased systemic inflammation, present in patients with nvAMD.