ArticleInvestigative ophthalmology & visual science2014
Age-related changes of cystatin C expression and polarized secretion by retinal pigment epithelium: potential age-related macular degeneration links.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Potential Causal Effects of Cystatin C on Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.Biomedicines · 2025Article
- Control of blood pressure and blood glucose levels has important clinical significance to the retina.BMC ophthalmology · 2025Article
- Cellular Characterization and Interspecies Evolution of the Tree Shrew Retina across Postnatal Lifespan.Research (Washington, D.C.) · 2024Article
- Loss of cystatin C regulates permeability and inflammatory pathways in retina.Microvascular research · 2023Article
- Article
- Intercellular communication analysis of the human retinal pigment epithelial and choroidal cells predicts pathways associated with aging, cellular senescence and age-related macular degeneration.Frontiers in aging neuroscience · 2022Article
- RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription.Journal of cellular and molecular medicine · 2021Article
- Transcriptomic Profiling of Human Pluripotent Stem Cell-derived Retinal Pigment Epithelium over Time.Genomics, proteomics & bioinformatics · 2021Article
- Genetics of 35 blood and urine biomarkers in the UK Biobank.Nature genetics · 2021Article
- Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration.Progress in retinal and eye research · 2020Review
- The aging lysosome: An essential catalyst for late-onset neurodegenerative diseases.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- Increased Rate of Retinal Pigment Epithelial Cell Migration and Pro-Angiogenic Potential Ensuing From Reduced Cystatin C Expression.Investigative ophthalmology & visual science · 2020Article
- Integrated Microarray and RNAseq Transcriptomic Analysis of Retinal Pigment Epithelium/Choroid in Age-Related Macular Degeneration.Frontiers in cell and developmental biology · 2020Article
- The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain.Cells · 2019Review
- 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
- The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- A convenient protocol for establishing a human cell culture model of the outer retina.F1000Research · 2018Article
- Comparative proteomic analysis of human embryonic stem cell-derived and primary human retinal pigment epithelium.Scientific reports · 2017Article
- Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2017Article
- Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration.Progress in retinal and eye research · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeCystatin C, a potent cysteine proteinase inhibitor, is abundantly secreted by the RPE and may contribute to regulating protein turnover in the Bruch's membrane (BrM). A cystatin C variant associated with increased risk of developing AMD and Alzheimer's disease (AD) presents reduced secretion levels from RPE. The purpose of this study was to analyze the effects of age and the accumulation of advanced glycation end-products (AGEs) on the expression and secretion of cystatin C by the RPE.
methodsConfluent monolayers of human fetal RPE (hfRPE) cells were cultured using an in vitro model mimicking extracellular AGE accumulation. Cystatin C expression, secretion, and its polarity were analyzed following culture on AGE-containing BrM mimics (AGEd versus non-AGEd). Monolayer barrier properties were assessed by transepithelial resistance measurements. The relative level of cystatin C protein expression in human RPE in situ was assessed immunohistochemically in relation to age.
resultsAdvanced glycation end product-exposed RPE monolayers presented significantly decreased cystatin C expression and secretion. Basolateral secretion was fully established by week 8 in non-AGEd conditions. In AGEd cultures, polarity of secretion was impaired despite maintenance of physiological barrier properties of the monolayer. In the macula region of RPE/choroid segments from human eyes, the level of cystatin C protein was reduced with increasing donor age.
conclusionsExposure to AGEs reduces expression of cystatin C and affects its normal secretion in cultured RPE. Age-related changes of cystatin C in the RPE from the posterior pole may compromise its extracellular functions, potentially contributing to AMD pathogenesis.
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