ArticlePloS one2011
Overexpression of HTRA1 leads to ultrastructural changes in the elastic layer of Bruch's membrane via cleavage of extracellular matrix components.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Cumulative association between age-related macular degeneration and less studied genetic variants in PLEKHA1/ARMS2/HTRA1: a meta and gene-cluster analysis.Molecular biology reports · 2013Pooled it
- Interactions Between Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration.Ophthalmology science · 2026Review
- Differential regulation of myopia progression by ON and OFF stimulation in guinea pigs.Eye and vision (London, England) · 2026Article
- Review
- Molecular Crosstalk in Age-Related Macular Degeneration: Integrating Oxidative Stress, Inflammation, microRNAs, and Genetic Susceptibility Toward Precision Therapeutics.Biomolecules · 2026Review
- Translational Molecular and Fluid Biomarkers for Age-Related Macular Degeneration: Practical Insights from Animal Models and Humans.Biomolecules · 2025Review
- HTRA1-dependent proteolysis induces age-related retinal degeneration and exacerbates choroidal neovascularization.Disease models & mechanisms · 2025Article
- Select Azo Compounds Post-translationally Modulate HTRA1 Abundance and Activity Potentially through Interactions at the Trimer Interface.ACS chemical biology · 2025Article
- Role of alpha-1 antitrypsin in Bruch's membrane integrity.Scientific reports · 2025Article
- Article
- The hypothetical molecular mechanism of the ethnic variations in the manifestation of age-related macular degeneration; focuses on the functions of the most significant susceptibility genes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Review
- Drug Approval for the Treatment of Geographic Atrophy: How We Got Here and Where We Need to Go.American journal of ophthalmology · 2024Review
- Modeling complex age-related eye disease.Progress in retinal and eye research · 2024Review
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- Article
- Intravitreal injection of fibrillin 2 (Fbn2) recombinant protein for therapy of retinopathy in a retina-specific Fbn2 knock-down mouse model.Scientific reports · 2023Article
- Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2023Review
- Development and validation of risk prediction and neural network models for dilated cardiomyopathy based on WGCNA.Frontiers in medicine · 2023Article
- Elastin turnover in ocular diseases: A special focus on age-related macular degeneration.Experimental eye research · 2022Review
- Polymorphism rs11200638 enhanced HtrA1 responsiveness and expression are associated with age-related macular degeneration.Eye (London, England) · 2022Article
24 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Variants in the chromosomal region 10q26 are strongly associated with an increased risk for age-related macular degeneration (AMD). Two potential AMD genes are located in this region: ARMS2 and HTRA1 (high-temperature requirement A1). Previous studies have suggested that polymorphisms in the promotor region of HTRA1 result in overexpression of HTRA1 protein. This study investigated the role of HTRA1 overexpression in the pathogenesis of AMD. Transgenic Htra1 mice overexpressing the murine protein in the retinal pigment epithelium (RPE) layer of the retina were generated and characterized by transmission electron microscopy, immunofluorescence staining and Western Blot analysis. The elastic layer of Bruch's membrane (BM) in the Htra1 transgenic mice was fragmented and less continuous than in wild type (WT) controls. Recombinant HTRA1 lacking the N-terminal domain cleaved various extracellular matrix (ECM) proteins. Subsequent Western Blot analysis revealed an overexpression of fibronectin fragments and a reduction of fibulin 5 and tropoelastin in the RPE/choroid layer in transgenic mice compared to WT. Fibulin 5 is essential for elastogenesis by promoting elastic fiber assembly and maturation. Taken together, our data implicate that HTRA1 overexpression leads to an altered elastogenesis in BM through fibulin 5 cleavage. It highlights the importance of ECM related proteins in the development of AMD and links HTRA1 to other AMD risk genes such as fibulin 5, fibulin 6, ARMS2 and TIMP3.
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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.