Dataset Information

Proteomics of vitreous humor of patients with exudative age-related macular degeneration.

ABSTRACT:

Background

There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).

Methods and findings

Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.

Conclusions

Proteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.

SUBMITTER: Koss MJ

PROVIDER: S-EPMC4020801 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Proteomics of vitreous humor of patients with exudative age-related macular degeneration.

Koss Michael Janusz MJ Hoffmann Janosch J Nguyen Nauke N Pfister Marcel M Mischak Harald H Mullen William W Husi Holger H Rejdak Robert R Koch Frank F Jankowski Joachim J Krueger Katharina K Bertelmann Thomas T Klein Julie J Schanstra Joost P JP Siwy Justyna J

PloS one 20140514 5

<h4>Background</h4>There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).<h4>Methods and findings</h4>Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Ninetee ...[more]

PMID: 24828575

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Project description:ImportanceSince the advent of optical coherence tomography angiography (OCT-A), nonexudative neovascularization has been described in the fellow eyes of unilateral exudative age-related macular degeneration (AMD). However, there is limited literature describing the natural course and optimal management of these lesions.ObjectiveTo determine the incidence of fellow eye involvement in patients presenting with unilateral typical AMD or polypoidal choroidal vasculopathy and to evaluate the patterns of OCT-A changes within 6 months before the onset of exudative changes, especially focusing on nonexudative neovascularization.Design, setting, and participantsData for this study were taken from a prospective, observational cohort study involving Asian patients with exudative AMD in the Asian AMD Phenotyping Study between October 2015 and March 2016. Analyses began in June 2017. Only patients who had gradable OCT-A and indocyanine green angiography (ICGA) scans of the fellow eye at baseline and follow-up at least 6 months apart were included for the analysis. The contralateral eye was evaluated for presence of nonexudative neovascularization based on multimodal imaging, which included ICGA, spectral domain optical coherence tomography, and OCT-A.Main outcomes and measuresThe difference between the incidence of those with nonexudative choroidal neovascularization and those without as analyzed using log-rank test and qualitative analysis of OCT-A images.ResultsWe included 95 fellow eyes of 95 patients who presented with unilateral exudative AMD with a mean (SD) age of 68.6 (8.6) years. Nonexudative neovascularization was present in 18 eyes (19%) (8 [22.9%] and 10 [19.0%] fellow eyes with typical AMD and polypoidal choroidal vasculopathy, respectively; 8 [44.4%] on OCT-A; 5 [27.8%] on ICGA; and 5 [27.8%] on both OCT-A and ICGA). Development of exudative changes was noted in 6 fellow eyes (6.3%). Four eyes developed exudation from previously noted nonexudative neovascularization, and 2 eyes arose exudative changes from de novo. The probability of developing exudation within 6 months was significantly higher in eyes with baseline nonexudative neovascularization (0.087; 95% CI, 0.0033-0.210) compared with eyes without (0.010; 95% CI, 0.0026-0.041) (P = .008). In all eyes whose OCT-A images were available immediately before the onset of exudative changes, there was an increase in the size of network vessels compared with baseline.Conclusions and relevanceThe presence of nonexudative neovascularization may predispose to the development of exudative changes.

Project description:Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and a useful platform for developing new therapies.

Dataset Information

Proteomics of vitreous humor of patients with exudative age-related macular degeneration.

Background

Methods and findings

Conclusions

Publications

Proteomics of vitreous humor of patients with exudative age-related macular degeneration.

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