Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging

Abstract

Objective: Systemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been studied. The aim of this study was to determine if there is a difference in plasma complement factor levels in intermediate AMD compared with controls, and if complement levels are related to the presence of RPD.

Methods and analysis: Levels of complement factors C1q (µg/mL), C4 (µg/mL), C2 (µg/mL), Mannose Binding Lectin (ng/mL), C4b (µg/mL), C3 (µg/mL), factor B (µg/mL), factor D (µg/mL), properdin (µg/mL), C3a (ng/mL), iC3b/C3b (ng/mL), Ba (ng/mL), factor H (µg/mL), factor I (µg/mL), C5 (µg/mL), C5a (pg/mL) and SC5b-9 (ng/mL) were measured in plasma.

Results: 109 cases and 65 controls were included in the study. Thirty-nine (36%) cases had RPD. Significantly lower systemic levels of: C1q (OR 0.96, 95% CI 0.94 to 0.98), factor B (OR 0.98, 95% CI 0.96 to 0.99), iC3b/C3b (OR 0.97, 95% CI 0.95 to 0.98), factor H (OR 0.99, 95% CI 0.98 to 0.99), factor I (OR 0.83, 95% CI 0.77 to 0.89) and C5 (OR 0.94, 95% CI 0.90 to 0.98) were found in cases versus controls. Significantly elevated levels of: C2 (OR 1.29, 95% CI 1.07 to 1.59), C3a (OR 1.03, 95% CI 1.01 to 1.05) Ba (OR 1.03, 95% CI 1.01 to 1.05) and C5a (OR 1.04, 95% CI 1.02 to 1.07) were found in cases versus controls. Systemic levels of complement factors measured were not related to the presence of RPD.

Conclusions: Levels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.

Keywords: epidemiology; immunology; inflammation; macula; retina.

Figure 1

The complement pathways, triggers for activation and analytes measured. The complement system has three activation pathways, classical, lectin and alternative. These three pathways are activated differently but all connect at the central point C3. The three pathways are interrelated by the action of alternative pathway as an amplification loop for the classical and lectin pathways. After C3, the complement system enters the terminal pathway, culminating in the membrane attached complex (also known as C5b-9). As activation flows through the cascade, the components are cleaved yielding activation fragments that are released into circulation. The components and activation fragments measured in this study are designated with a frame and encompass the whole cascade. CRP, C reactive protein; DAMP, damage-associated molecular pattern; PAMP, pathogen-associated molecular pattern; MBL, Mannose Binding Lectin.