Article

Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction and the 20-Year Cumulative Incidence of Early Age-Related Macular Degeneration The Beaver Dam Eye Study

Jama Ophthalmology (Impact Factor: 3.83). 01/2014; 132(4). DOI: 10.1001/jamaophthalmol.2013.7671
Source: PubMed

ABSTRACT Importance
Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons.Objective
To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD.Design, Setting, and Participants
This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010.Exposures
Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor–α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule–1 and soluble intercellular adhesion molecule–1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs.Main Outcomes and Measures
Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD.Results
The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor–α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule–1 (odds ratio per SD on the logarithmic scale, 1.21; P = .04).Conclusions and Relevance
We found modest evidence of relationships of serum high-sensitivity C-reactive protein, tumor necrosis factor–α receptor 2, interleukin-6, and soluble vascular cell adhesion molecule–1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors. It is not known whether these associations represent a cause and effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.

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    • "Interestingly, APOA-I and APOE can also extract membrane cholesterol from lipid rafts, activate the innate immunity receptor cluster in the absence of TLR ligands, and induce several inflammatory cytokines including IL-6 (shown for APOA-I) (Smoak et al, 2010). Recently, it has been shown that increased IL-6 levels are associated with AMD incidence (Klein et al, 2014) and with late AMD (Seddon et al, 2005; Klein et al, 2008). It is currently not clear how APOE and IL-6 participate in AMD patho- genesis. "
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