Comparative proteomic study in serum of patients with primary open-angle glaucoma and pseudoexfoliation glaucoma

González‐Iglesias, Héctor; Álvarez, Lydia; García, Montserrat; Escribano, Julio; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega, Luís; Coca‐Prados, Miguel

doi:10.1016/j.jprot.2013.12.006

Cited by 40 publications

(55 citation statements)

References 28 publications

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“…109,110 Proteomic analyses in aqueous humor and serum mainly found proteins related to inflammation and oxidative stress to be differentially expressed in POAG and PEXG patients. [111][112][113] The higher presence of immune-related proteins in serum of glaucoma patients was already known, and serum antibodies with target antigens in eye tissues were the main proteins screened for biomarker discovery in the past. 114 Recently, proteomic studies characterized glaucoma-specific proteomes in tears, which might be an interesting source to further explore in the future, particularly because of the noninvasive nature of tear collection.…”

Section: Glaucomamentioning

confidence: 99%

Omics Biomarkers in Ophthalmology

Jong

Lefeber

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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''Omics'' refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes. We observe that genomic analyses were mainly successful in AMD research (almost half of the genomic heritability has been explained), whereas large parts of disease variability or risk remain unsolved in most of the other diseases. Other omics studies like transcriptomics, proteomics, and metabolomics provided additional candidate proteins and pathways for several eye diseases, although sample sizes in these studies were often very small and replication is lacking. In order to translate omics results into clinical biomarkers, larger sample sizes and validation across different cohorts would be essential. In conclusion, omicsbased studies are increasing in ophthalmology, and further application to the clinic might develop in the years to come. Integration of genomics with other type of omics data has the potential to improve the accuracy of predictive tests. Moreover, in the future, omics may lead to stratification of patients into subgroups based on molecular profiles, enabling the development of personalized treatments.

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Section: Glaucomamentioning

confidence: 99%

Omics Biomarkers in Ophthalmology

Jong

Lefeber

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of aqueous humor proteins associated with cataract development

Xiao

et al. 2015

Clinical Biochemistry

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“…Systemic PEX material is often found in the periphery of blood vessels and may originate from fibroblasts and muscle cells(12). Proteomic analysis of serum from PEXG shows elevated levels of elastic fiber proteins such as vitronectin and fibulin compared to control patients(24, 25). Interestingly, the levels of various complement factors and other immune-related proteins are also elevated in the serum of PEXG patients, but not significantly greater to those in serum from primary open angle glaucoma (POAG) patients(24).…”

Section: Pex Materials Compositionmentioning

confidence: 92%

“…Proteomic analysis of serum from PEXG shows elevated levels of elastic fiber proteins such as vitronectin and fibulin compared to control patients(24, 25). Interestingly, the levels of various complement factors and other immune-related proteins are also elevated in the serum of PEXG patients, but not significantly greater to those in serum from primary open angle glaucoma (POAG) patients(24). Also, apolipoproteins, complement factors, and other cytokines have been connected with other diseases of aging including age-related macular degeneration, atherosclerosis, cardiovascular disease, and Alzheimer’s disease(24).…”

Section: Pex Materials Compositionmentioning

confidence: 92%

Genomic and Proteomic Pathophysiology of Pseudoexfoliation Glaucoma

Porta¹,

Lee²

2014

International Ophthalmology Clinics

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PEX stems from a pathologic elastotic process involving the cross-linking gene lysyl oxidase-like-1 (LOXL1), and is associated with abnormal formation of elastic extracellular matrix. We previously described a protein sink model to explain PEX material deposition on the lens capsule and other intraocular surfaces. Recent research findings not only provide evidence to support this hypothesis, but also further our understanding of the fundamental disease process. A key aspect of the pathogenic process is the compromise of blood-aqueous barrier integrity in PEXG. Decreased level of LOXL1 is associated with decreased elastin incorporation into elastic tissues, including the elastic lamina of blood vessels. This results in unincorporated elastin that is released as soluble elastin, and leakage of serum proteins, inflammatory cytokines, and extracellular matrix components into aqueous humor. This ultimately leads to aggregation and precipitation of large protein complexes, or PEX material, throughout intraocular surfaces as described in the protein sink model. The pathologic PEX process also affects the biomechanical properties of elastic tissues, such as the trabecular meshwork, lens zonules, and lamina cribrosa. This may be part of the primary pathologic process with intrinsically altered extracellular matrix proteins. This fundamental change in the structural composition of these tissues may alter their rigidity, elasticity, and other biomechanical properties. This likely contributes to increased trabecular meshwork outflow resistance and high intraocular pressure, and mechanical injury to retinal ganglion cell axons at the lamina cribrosa, which are conducive to glaucoma. These pathophysiologic processes combined may underlie some of the clinical hallmarks observed in PEXG.

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Comparative proteomic study in serum of patients with primary open-angle glaucoma and pseudoexfoliation glaucoma

Cited by 40 publications

References 28 publications

Omics Biomarkers in Ophthalmology

Omics Biomarkers in Ophthalmology

Proteomic analysis of aqueous humor proteins associated with cataract development

Genomic and Proteomic Pathophysiology of Pseudoexfoliation Glaucoma

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