ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2012
Proteomic profiling of human retinal pigment epithelium exposed to an advanced glycation-modified substrate.
Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Novel Possible Protein Targets in Neovascular Age-Related Macular Degeneration: A Pilot Study Experiment.Frontiers in medicine · 2021Article
- Advanced glycation end products-related modulation of cathepsin L and NF-κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα.Journal of cellular and molecular medicine · 2019Article
- Proteomics of Human Retinal Pigment Epithelium (RPE) Cells.Proteomes · 2018Review
- A local complement response by RPE causes early-stage macular degeneration.Human molecular genetics · 2015Article
- Oxidative stress protection by exogenous delivery of rhHsp70 chaperone to the retinal pigment epithelium (RPE), a possible therapeutic strategy against RPE degeneration.Pharmaceutical research · 2015Article
- NLRP3 inflammasome: activation and regulation in age-related macular degeneration.Mediators of inflammation · 2015Review
- Age-related changes of cystatin C expression and polarized secretion by retinal pigment epithelium: potential age-related macular degeneration links.Investigative ophthalmology & visual science · 2014Article
- Aging is not a disease: distinguishing age-related macular degeneration from aging.Progress in retinal and eye research · 2013Review
- The ubiquitin-proteasome system in retinal health and disease.Molecular neurobiology · 2013Review
- Retinal microenvironment imbalance in dry age-related macular degeneration: a mini-review.Gerontology · 2013Review
- Complement dysregulation in AMD: RPE-Bruch's membrane-choroid.Molecular aspects of medicine · 2012Review
- Mechanisms of age-related macular degeneration.Neuron · 2012Review
- Mechanisms for countering oxidative stress and damage in retinal pigment epithelium.International review of cell and molecular biology · 2012Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThe retinal pigment epithelium (RPE) and underlying Bruch's membrane undergo significant modulation during ageing. Progressive, age-related modifications of lipids and proteins by advanced glycation end products (AGEs) at this cell-substrate interface have been implicated in RPE dysfunction and the progression to age-related macular degeneration (AMD). The pathogenic nature of these adducts in Bruch's membrane and their influence on the overlying RPE remains unclear. This study aimed to identify alterations in RPE protein expression in cells exposed to AGE-modified basement membrane (AGE-BM), to determine how this "aged" substrate impacts RPE function and to map the localisation of identified proteins in ageing retina.
methodsConfluent ARPE-19 monolayers were cultured on AGE-BM and native, non-modified BM (BM). Following 28-day incubation, the proteome was profiled using 2-dimensional gel electrophoresis (2D), densitometry and image analysis was employed to map proteins of interest that were identified by electrospray ionisation mass spectrometry (ESI MS/MS). Immunocytochemistry was employed to localise identified proteins in ARPE-19 monolayers cultured on unmodified and AGE-BM and to analyze aged human retina.
resultsImage analysis detected altered protein spot densities between treatment groups, and proteins of interest were identified by LC ESI MS/MS which included heat-shock proteins, cytoskeletal and metabolic regulators. Immunocytochemistry revealed deubiquitinating enzyme ubiquitin carboxyterminal hydrolase-1 (UCH-L1), which was upregulated in AGE-exposed RPE and was also localised to RPE in human retinal sections.
conclusionsThis study has demonstrated that AGE-modification of basement membrane alters the RPE proteome. Many proteins are changed in this ageing model, including UCHL-1, which could impact upon RPE degradative capacity. Accumulation of AGEs at Bruch"s membrane could play a significant role in age-related dysfunction of the RPE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.