Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration

Kersten, Eveline; Paun, Constantin C.; Schellevis, Rosa L.; Hoyng, Carel B.; Delcourt, Cécile; Lengyel, Imre; Pető, Tünde; Ueffing, Marius; Klaver, Caroline C.W.; Dammeier, Sascha; Hollander, Anneke I. den; Jong, Eiko K. de

doi:10.1016/j.survophthal.2017.05.003

Cited by 102 publications

(127 citation statements)

References 365 publications

(637 reference statements)

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“…TGF‐β is found to increase the expression of VEGF and is therefore also implicated as an angiogenic factor . Cross‐sectional studies found conflicting results whether measurements of systemic and local angiogenic factors differ between AMD patients and controls . Currently, there are no prospective cohorts that have measured angiogenic factors to predict disease progression in AMD.…”

Section: Molecular Risk Factorsmentioning

confidence: 99%

“…LDL are lipoproteins (see section Lipoproteins) that are an easy target for oxidation by free radicals. While some cross‐sectional studies show increased levels of systemic ox‐LDL in AMD patients, only two prospective cohorts have investigated the relationship between systemic ox‐LDL and disease progression and found no correlation …”

Section: Molecular Risk Factorsmentioning

confidence: 99%

“…Although the complement system acts locally in AMD, its components can also be measured systemically. Many case‐control studies have found differences in expression levels of systemic complement regulators and components between AMD patients and controls . However, it is not clear if systemic activation levels influence and/or reflect local complement activation in AMD.…”

Section: Molecular Risk Factorsmentioning

confidence: 99%

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Risk factors for progression of age‐related macular degeneration

Heesterbeek

Lorés‐Motta

Hoyng

et al. 2020

Ophthalmic Physiologic Optic

194

185

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Purpose Age‐related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare. Recent findings While phenotypic risk factors such as drusen and pigment abnormalities become more important to predict disease progression during the course of the disease, demographic, environmental, genetic and molecular risk factors are more valuable at earlier disease stages. Demographic and environmental risk factors such as age and smoking are consistently reported to be related to disease progression, while other factors such as sex, body mass index (BMI) and education are less often associated. Of all known AMD variants, variants that are most consistently reported with disease progression are rs10922109 and rs570618 in CFH, rs116503776 in C2/CFB/SKIV2L, rs3750846 in ARMS2/HTRA1 and rs2230199 in C3. However, it seems likely that other AMD variants also contribute to disease progression but to a lesser extent. Rare variants have probably a large effect on disease progression in highly affected families. Furthermore, current prediction models do not include molecular risk factors, while these factors can be measured accurately in the blood. Possible promising molecular risk factors are High‐Density Lipoprotein Cholesterol (HDL‐C), Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), zeaxanthin and lutein. Summary Phenotypic, demographic, environmental, genetic and molecular risk factors can be combined in prediction models to predict disease progression, but the selection of the proper risk factors for personalised risk prediction will differ among individuals and is dependent on their current disease stage. Future prediction models should include a wider set of genetic variants to determine the genetic risk more accurately, and rare variants should be taken into account in highly affected families. In addition, adding molecular factors in prediction models may lead to preventive strategies and personalised advice.

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Section: Molecular Risk Factorsmentioning

confidence: 99%

Section: Molecular Risk Factorsmentioning

confidence: 99%

Section: Molecular Risk Factorsmentioning

confidence: 99%

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Risk factors for progression of age‐related macular degeneration

Heesterbeek

Lorés‐Motta

Hoyng

et al. 2020

Ophthalmic Physiologic Optic

194

185

View full text Add to dashboard Cite

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“…Choroidal neovascularization (CNV) is a major characteristic of wet age-related macular degeneration (AMD) and is one of the most common causes of irreversible blindness in people over 60 years old in western countries [1]. Recent studies indicate that CNV is a complex process in which the degeneration of retinal blood vessels in the elderly leads to tissue ischemia and hypoxia; therefore, hypoxia-mediated signaling is thought to be involved in the progression of the wet form of AMD [2].…”

Section: Introductionmentioning

confidence: 99%

Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells

Sun¹,

Cai²,

Liu³

2017

Cell Physiol Biochem

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Background/Aims: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. Methods: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002). The anti-proliferative effect of celecoxib was assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed to detect the levels of PI3K, phosphorylated AKT (p-AKT), HIF-1α, VEGF and COX-2. Results: Celecoxib inhibited the proliferation of RPE cells in a dose-dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA and protein levels and decreased HIF-1α protein expression. HIF-1α activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down-regulation of HIF-1α and VEGF required the suppression of the hypoxia-induced PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells treated with celecoxib. Conclusions: The antiangiogenic effects of celecoxib in RPE cells under hypoxic conditions resulted from the inhibition of HIF-1α and VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT-dependent pathway.

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“…In the classical view, the RPE, including the Bruch's membrane (BM), was the only pathological site to be considered in AMD. However, more recent data strongly suggest a much more active role of the choroid, photoreceptors, and the blood system in the development of AMD than previously thought (6)(7)(8). A main stream AMD hypothesis is that nonpathalogical agerelated retinal changes insidiously turn in into pathological (dry) AMD changes, while a more sudden twist on top of the ongoing pathology causes (wet) AMD (9,10).…”

Section: 2mentioning

confidence: 99%