Evidence map›Paper›PMID 38168310›Full record

ArticlebioRxiv : the preprint server for biology2023

GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.

Sophia M DiCesare, Antonio J Ortega, Gracen E Collier, Steffi Daniel, Krista N Thompson, Melissa K McCoy, Bruce A Posner, John D Hulleman

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Sophia M DiCesareDepartment of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75390, United States.
Antonio J OrtegaDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6 St. SE, Minneapolis, Minnesota, 55455, United States.
Gracen E CollierDepartment of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75390, United States.
Steffi DanielDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6 St. SE, Minneapolis, Minnesota, 55455, United States.
Krista N ThompsonDepartment of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75390, United States.
Melissa K McCoyDepartment of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, United States.
Bruce A PosnerDepartment of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, United States.
John D HullemanDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, 2001 6 St. SE, Minneapolis, Minnesota, 55455, United States.ORCID 0000-0001-8149-656X
The University of Texas Southwestern Medical Center · USUniversity of Minnesota · US

Funding

Stem Cell, Organoid and Cell Phenotyping ModuleP30EY030413 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI W MATTHEW PETROLL · 2019 to 2026
$5.9M
Supplement to Promote Diversity in Health-Related Research - Prevention of macular pathophysiology...Parent GrantR01EY027785 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI John Douglas Hulleman · 2018 to 2026
$2.8M
NEI NIH HHS P30 EY030413NEI NIH HHS R01 EY027785
6 · The paper itself

Abstract

Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD) is an age-related macular degeneration (AMD)-like retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production from retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus which enabled simple, sensitive, and high throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix (ECM), reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium derived factor). In vivo, treatment of 8 mo R345W

Indexed as

AMDCHIR99021DHRDEFEMP1F3fibulin-3glycogen synthase kinase 3ML

Identifiers

PMID38168310
PMCPMC10760106
OpenAlexW4389777847

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.