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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Targeting Hif1a rescues cone degeneration and prevents subretinal neovascularization in a model of chronic hypoxia
|
|---|---|
| Published in |
Molecular Neurodegeneration, March 2018
|
| DOI | 10.1186/s13024-018-0243-y |
| Pubmed ID | |
| Authors |
Maya Barben, Christian Schori, Marijana Samardzija, Christian Grimm |
| Abstract |
Degeneration of cone photoreceptors leads to loss of vision in patients suffering from age-related macular degeneration (AMD) and other cone dystrophies. Evidence, such as choroidal ischemia and decreased choroidal blood flow, implicates reduced tissue oxygenation in AMD pathology and suggests a role of the cellular response to hypoxia in disease onset and progression. Such a chronic hypoxic situation may promote several cellular responses including stabilization of hypoxia-inducible factors (HIFs). To investigate the consequence of a chronic activation of the molecular response to hypoxia in cones, von Hippel Lindau protein (VHL) was specifically ablated in cones of the all-cone R91W;Nrl -/- mouse. Retinal function and morphology was evaluated by ERG and light microscopy, while differential gene expression was tested by real-time PCR. Retinal vasculature was analyzed by immunostainings and fluorescein angiography. Two-way ANOVA with Šídák's multiple comparison test was performed for statistical analysis. Cone-specific ablation of Vhl resulted in stabilization and activation of hypoxia-inducible factor 1A (HIF1A) which led to increased expression of genes associated with hypoxia and retinal stress. Our data demonstrate severe cone degeneration and pathologic vessel growth, features that are central to AMD pathology. Subretinal neovascularization was accompanied by vascular leakage and infiltration of microglia cells. Interestingly, we observed increased expression of tissue inhibitor of metalloproteinase 3 (Timp3) during the aging process, a gene associated with AMD and Bruch's membrane integrity. Additional deletion of Hif1a protected cone cells, prevented pathological vessel growth and preserved vision. Our data provide evidence for a HIF1A-mediated mechanism leading to pathological vessel growth and cone degeneration in response to a chronic hypoxia-like situation. Consequently, our results identify HIF1A as a potential therapeutic target to rescue hypoxia-related vision loss in patients. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 8 | 24% |
| Student > Master | 5 | 15% |
| Researcher | 4 | 12% |
| Student > Ph. D. Student | 4 | 12% |
| Student > Doctoral Student | 3 | 9% |
| Other | 2 | 6% |
| Unknown | 8 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 29% |
| Agricultural and Biological Sciences | 5 | 15% |
| Neuroscience | 4 | 12% |
| Medicine and Dentistry | 3 | 9% |
| Nursing and Health Professions | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 9 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 March 2018.
All research outputs
#18,590,133
of 23,026,672 outputs
Outputs from Molecular Neurodegeneration
#792
of 854 outputs
Outputs of similar age
#258,490
of 332,611 outputs
Outputs of similar age from Molecular Neurodegeneration
#17
of 17 outputs
Altmetric has tracked 23,026,672 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 854 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.