ArticleInvestigative ophthalmology & visual science2010
Identification of novel substrates for the serine protease HTRA1 in the human RPE secretome.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.Ophthalmology · 2012Pooled it
- Endothelial NOX4‑driven oxidative stress inhibition reverses HtrA1 deficiency‑induced blood‑brain barrier disruption and cognitive impairment.International journal of molecular medicine · 2026Article
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- HTRA1 and complement activation in neovascular age-related macular degeneration.Japanese journal of ophthalmology · 2025Article
- Article
- Altered Elastin Turnover, Immune Response, and Age-Related Retinal Thinning in a Transgenic Mouse Model With RPE-Specific HTRA1 Overexpression.Investigative ophthalmology & visual science · 2024Article
- Modeling complex age-related eye disease.Progress in retinal and eye research · 2024Review
- Article
- SEPDB: a database of secreted proteins.Database : the journal of biological databases and curation · 2024Article
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease.Research square · 2023Article
- Human retinal secretome: A cross-link between mesenchymal and retinal cells.World journal of stem cells · 2023Review
- A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration.Cell genomics · 2023Article
- CRISPR editing demonstrates rs10490924 raised oxidative stress in iPSC-derived retinal cells from patients withProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2023Review
- The emerging role of the HTRA1 protease in brain microvascular disease.Frontiers in dementia · 2023Review
- Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.Journal of clinical neurology (Seoul, Korea) · 2023Review
- Proteomic profiling in cerebral amyloid angiopathy reveals an overlap with CADASIL highlighting accumulation of HTRA1 and its substrates.Acta neuropathologica communications · 2022Article
- APP deficiency and HTRA2 modulates PrPBBA advances · 2022Article
- Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration.Experimental eye research · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
PURPOSE. To define the role of the serine protease HTRA1 in age-related macular degeneration (AMD) by examining its expression level and identifying its potential substrates in the context of primary RPE cell extracellular milieu. METHODS. Primary RPE cell cultures were established from human donor eyes and screened for CFH, ARMS2, and HTRA1 risk genotypes by using an allele-discrimination assay. HTRA1 expression in genotyped RPE cells was determined by using real-time PCR and quantitative proteomics. Potential HTRA1 substrates were identified by incubating RPE-conditioned medium with or without human recombinant HTRA1. Selectively cleaved proteins were quantified by using the differential stable isotope labeling by amino acids in cell culture (SILAC) strategy. RESULTS. HTRA1 mRNA levels were threefold higher in primary RPE cells homozygous for the HTRA1 promoter risk allele than in RPE cells with the wild-type allele, which translated into a twofold increase in HTRA1 secretion by RPE cells with the risk genotype. A total of 196 extracellular proteins were identified in the RPE secretome, and only 8 were found to be selectively cleaved by the human recombinant HTRA1. These include fibromodulin with 90% cleavage, clusterin (50%), ADAM9 (54%), vitronectin (54%), and alpha2-macroglobulin (55%), as well as some cell surface proteins including talin-1 (21%), fascin (40%), and chloride intracellular channel protein 1 (51%). CONCLUSIONS. Recombinant HTRA1 cleaves RPE-secreted proteins involved in regulation of the complement pathway (clusterin, vitronectin, and fibromodulin) and of amyloid deposition (clusterin, alpha2-macroglobulin, and ADAM9). These findings suggest a link between HTRA1, complement regulation, and amyloid deposition in AMD pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.