Systemic levels of interleukin‐6 in patients with age‐related macular degeneration: a systematic review and meta‐analysis

Abstract

Age-related macular degeneration (AMD) is the most prevalent cause of irreversible vision loss in industrialized countries. Several studies have investigated systemic interleukin-6 (IL-6) levels of patients with AMD. In this study, we systemically reviewed the literature to provide an overview of the field and used meta-analyses to provide a summary estimate of the standardized mean difference (SMD) of systemic IL-6 between patients with AMD and control individuals. We searched the literature databases PubMed/MEDLINE, Embase, Web of Science and the Cochrane Central on 1 June 2019 for relevant studies on humans. Two authors independently extracted data and evaluated risk of bias. We identified 19 studies for the qualitative review with a total of more than 3586 individuals (1865 controls and 1721 with AMD). We found an overall randomeffects SMD in systemic IL-6 levels 0.63 (95% CI: 0.28 to 0.99, p = 0.0005) corresponding to a medium effect size. In a subgroup analysis, we found that early AMD was not strongly associated with elevated IL-6 levels (0.12, 95% CI: À0.01 to 0.24, p = 0.06), which was in contrast to the significantly elevated IL-6 levels in patients with geographic atrophy (1.21, 95% CI: 0.41 to 2.01, p = 0.003) and patients with neovascular AMD (0.99, 95% CI: 0.34 to 1.63, p = 0.003). Our results show that the evidence today suggests an increased systemic IL-6 in patients with AMD, but that this may be a phenomenon more closely related to the late subtypes of AMD.

Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases

“…Additionally, aberrant vasculature present in retinopathy can be induced by AGEs and protein kinase C activation [ 45 ]. Finally, the effects of hyperglycemia on eye health may be mediated by systemic health conditions including dyslipidemia, which is associated with the formation of deleterious lipid droplets in the eye [ 48 ], as well as chronic low-grade inflammation, which triggers immune hyperactivity in retinal cells [ 49 ].…”

Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

“…A recent meta-analysis showed that a high level of plasma interleukin-6 (IL-6) is associated with neovascular AMD and geographic atrophy, suggesting that the late stages of AMD are accompanied by chronic low-grade inflammation and the therapeutic potential of targeting systemic IL-6 [ 22 ]. In AMD, drusen accumulation can also trigger inflammation, where inflammatory cells are then drawn to the retina [ 23 ].…”

Basolateral activation with TLR agonists induces polarized cytokine release and reduces barrier function in RPE in vitro

“…AMD is a multifactorial disease, of which systemic inflammation is discussed as a potentially major contributing factor. Studies show elevated systemic cytokine concentrations and inadequate systemic immune modulation [25][26][27][28][29]. In the retina, the RPE is in close contact with the choroid, and because of its sentinel function, it may react to systemic proinflammatory signals presented at the choroidal (basal) side, which may have consequences for the inflammatory milieu at the retinal (apical) side.…”