Systemic inflammation triggers local complement production in the mouse retina and RPE.

Systemic inflammation is increasingly recognized as a potential contributor in sight threatening retinal diseases such as Age-related Macular Degeneration (AMD). Yet, its impact on local eye immune responses and further pathological processes remains poorly understood. This study aims to elucidate the effect of peripheral immune activation on the local complement system, a central component of innate immunity with a dual role in maintaining ocular homeostasis and mediating inflammation, in the mouse retina and retinal pigment epithelium (RPE). Using a systemic lipopolysaccharide (LPS) challenge and a high-resolution proteomic approach, we observed a significant increase in complement factor 3 (C3) production in the RPE and retina 24 h post-injection. Further analysis confirmed the local source of complement signaling in resident cells such as astrocytes and RPE, independently from blood-retina barrier disruption. These findings reveal a direct cross-talk between systemic immune activation and ocular complement activation, and highlight the potential implications of systemic inflammation in the pathogenesis of ocular diseases, underlining the importance of future research into targeted therapies for inflammation-driven conditions.