Abstract

PurposeHigh-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients.MethodsBlood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants.ResultsIn our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01).ConclusionsThe investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis.

Highlights

  • Cholesterol maintenance in the retina is still poorly understood but needs to be studied to delineate the link between retinal cholesterol and age-related macular degeneration (AMD), an important cause of blindness in the elderly population

  • We observed that the High-density lipoproteins (HDL) associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p

  • The investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients

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Summary

Introduction

Cholesterol maintenance in the retina is still poorly understood but needs to be studied to delineate the link between retinal cholesterol and age-related macular degeneration (AMD), an important cause of blindness in the elderly population. High-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD) [1]. Conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels [2]. Likewise systemic levels of apolipoprotein A1 (apoA-I), the major protein component in HDL, were not associated with AMD [13]. There have been reports of HDL-related loci associated with AMD [3,4,5,6,14,15], some studies could not confirm these results [2,16,17]. Common genetic variants have been found on the cholesteryl ester transfer protein (CETP) gene, which promotes the transfer of cholesteryl-ester from HDL to very low-density and low-density lipoprotein (LDL), the hepatic lipase gene, which is involved in the metabolism of HDL, the apolipoprotein E (apoE) gene, an apolipoprotein of HDL, and the ATP-binding cassette transporter 1 gene, which mediates the efflux of cholesterol and phospholipids to poorly lipidated HDL [15,18,19]

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