Proteomics of Vitreous Humor of Patients with Exudative Age-Related Macular Degeneration

Abstract

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

Systems pathology analysis identifies neurodegenerative nature of age‐related vitreoretinal interface diseases

“…Mass spectrometry (MS)‐based quantitative proteomics provides a means for the determination of global proteome changes at the tissue and cellular levels, enabling a molecular level characterization of the pathophysiologies of complex eye disorders. Currently, most proteomic studies characterizing disease‐induced vitreous proteome changes have focused on proliferative and nonproliferative diabetic retinopathies (Kim et al, 2007; Loukovaara et al, 2015; Wang, Feng, Hu, Xie, & Wang, 2013), proliferative vitreoretinopathy (Garweg, Tappeneiner, & Halberstadt, 2013; Mitry, Fleck, Wright, Campbell, & Charteris, 2010), and age‐related macular degeneration (AMD; Koss et al, 2014), whereas iERM and MH remain less‐studied (Mandal et al, 2013; Pollreisz et al, 2013; Yu et al, 2014; Zhang et al, 2017). …”

Proteomic analysis of aqueous humor proteins associated with cataract development

“…Cataract is one of the most prevalent eye diseases, and numerous studies have been conducted to investigate the underlying mechanisms of cataract development for potential prevention and treatment strategies [1][2][3][4]. Many evidences have showed that age is the biggest risk factor [5].…”

Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration

“…Proteomics studies proteins at a large scale, and has been used in AMD research to study the protein content of drusen, macular, retinal, and RPE components, plasma, and eye fluids. [104][105][106][107][108][109][110][111] Epigenomics studies the methylation state of our DNA, which correlates to altered gene expression levels. These methylation patterns can be altered by our lifestyle, for example by smoking or by our diet.…”