Association between novel lipoprotein particles and age-related macular degeneration

Abstract

Purpose : Previous studies have shown an association between extra-large high-density lipoprotein (XL-HDL) levels in blood and age-related macular degeneration (AMD). In addition, there is increasing evidence to support a relationship between lipoproteins and the complement system, the major pathway in AMD pathogenesis. Recently, a novel lipoprotein fraction with a size between XL-HDL and low-density lipoprotein 4 (LDL IV), termed the midzone, was identified by ion mobility assay and found to be correlated with cardiovascular disease. We tested whether this midzone fraction is also associated with complement activation and AMD.

Methods : Plasma samples from 197 advanced AMD (60% women, mean (SD) age 74.93 yrs (9.52 yrs)) with 200 controls (59% women, mean (SD) age 73.59 yrs (9.64 yrs)) and 100 intermediate AMD patients (60% women, mean (SD) age 75.85 yrs (9.63 yrs)) with 102 controls (61% women, mean (SD) age 75.97 yrs (8.47 yrs)) were selected from our biobank. The lipoprotein spectrum was determined using an ion mobility assay. Complement activation levels determined as the C3d/C3 ratio were available for all samples, measured by rocket immunoelectrophoresis and radial immunodiffusion respectively. We performed linear regression analysis to assess associations in R using the PheWAS package.

Results : A significant association was observed between the midzone concentration and complement activation (in advanced AMD samples: p = 4.6 * 10^-5, R² = 0.13; in intermediate AMD samples: p = 1.9 * 10^-4, R² 0.14). Concentrations of the HDL-midzone boundary, a subfraction of the midzone, were also significantly increased in advanced AMD (median nmol/L (Q1-Q3): AMD 368.1 (316.3-427.5), controls 355.8 (307.1-401.8), p = 0.0328; corrected for age). No significant difference was found between intermediate AMD and controls (p = 0.959).

Conclusions : Novel midzone lipoprotein particles appear to play a role in complement activation and in risk for AMD, and may confer a link between XL-HDL and inflammation in AMD pathogenesis.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.