| Title |
Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells
|
|---|---|
| Published in |
Aging, February 2023
|
| DOI | 10.18632/aging.204522 |
| Pubmed ID | |
| Authors |
Tu Nguyen, Daniel Urrutia-Cabrera, Luozixian Wang, Jarmon G Lees, Jiang-Hui Wang, Sandy S C Hung, Alex W Hewitt, Thomas L Edwards, Sam McLenachan, Fred K Chen, Shiang Y Lim, Chi D Luu, Robyn Guymer, Raymond C B Wong |
| Abstract |
Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line ARPE-19 with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that it retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 caused a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2 in ARPE-19, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology. |
X Demographics
The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 4 | 40% |
| Unknown | 6 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 70% |
| Scientists | 2 | 20% |
| Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 5 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 2 | 40% |
| Student > Bachelor | 1 | 20% |
| Unknown | 2 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 1 | 20% |
| Neuroscience | 1 | 20% |
| Medicine and Dentistry | 1 | 20% |
| Unknown | 2 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 74. 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 11 June 2023.
All research outputs
#562,714
of 24,969,131 outputs
Outputs from Aging
#142
of 4,019 outputs
Outputs of similar age
#12,436
of 413,491 outputs
Outputs of similar age from Aging
#14
of 106 outputs
Altmetric has tracked 24,969,131 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,019 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.5. This one has done particularly well, scoring higher than 96% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 413,491 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 106 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.