Evidence map›Paper›PMID 31270273›Full record

ArticleScience translational medicine2019

Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy.

Hisashi Yokomizo, Yasutaka Maeda, Kyoungmin Park, Allen C Clermont, Sonia L Hernandez, Ward Fickweiler, Qian Li, Chih-Hao Wang, Samantha M Paniagua, Fabricio Simao and 13 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
11.1field-weighted citation impact, top 1% of its field
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

70 citing papers in PubMed, 87 citations in OpenAlex.

  1. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
    Review
  2. Article
  3. Article
  4. Observational
  5. Explaining Retinal Susceptibility to Diabetes Through Photoreceptor Biology.International journal of molecular sciences · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Diabetic retinal disease.Nature reviews. Disease primers · 2025
    Review
  14. Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 2 institutions in 1 country.

Hisashi YokomizoResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0001-7759-2014
Yasutaka MaedaResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0002-3259-5622
Kyoungmin ParkResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Allen C ClermontResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Sonia L HernandezResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0001-6188-0732
Ward FickweilerResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0002-6807-2532
Qian LiResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Chih-Hao WangResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Samantha M PaniaguaResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Fabricio SimaoResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Atsushi IshikadoResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Bei SunResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0003-0897-8831
I-Hsien WuResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0002-2563-7505
Sayaka KatagiriResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0002-5765-2742
David M PoberResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Liane J TinsleyResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0001-6959-2364
Robert L AveryCalifornia Retina Consultants, Santa Barbara, CA 93103, USA.
Edward P FeenerResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.
Timothy S KernCenter for Translational Vision Research, Gavin Herbert Eye Institute, Irvine, CA 92697, USA.ORCID 0000-0002-5694-6562
Hillary A KeenanResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0003-4172-5537
Lloyd Paul AielloResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0003-2012-3465
Jennifer K SunResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA.ORCID 0000-0003-0915-6303
George L KingResearch Division, Joslin Diabetes Center, Boston, MA 02215, USA. george.king@joslin.harvard.edu.ORCID 0000-0002-0335-5881
Joslin Diabetes Center · USCalifornia Retina Consultants · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Validation of Potential Protective Factors from Diabetic ComplicationsDP3DK094333 · NIDDK · JOSLIN DIABETES CENTER · PI KING, GEORGE L · 2011 to 2015
$4.1M
Identification of Retinoid-Binding Protein 3 (RBP3): A Protective Factor against Diabetic Retinopathy Using Retina from People with Extreme Duration of DiabetesR01EY026080 · NEI · JOSLIN DIABETES CENTER · PI KING, GEORGE L · 2016 to 2024
$3.1M
Pyruvate kinase M2 levels and activation as protective factors for diabetic nephropathyDP3DK112192 · NIDDK · JOSLIN DIABETES CENTER · PI KING, GEORGE L · 2016 to 2016
$2.3M
NEI NIH HHS R01 EY026080NIDDK NIH HHS DP3 DK094333NIDDK NIH HHS DP3 DK112192NIDDK NIH HHS P30 DK036836
6 · The paper itself

Abstract

The Joslin Medalist Study characterized people affected with type 1 diabetes for 50 years or longer. More than 35% of these individuals exhibit no to mild diabetic retinopathy (DR), independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients. Proteomic analysis of retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity. Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor (VEGF). Mechanistically, our results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and Müller cells. Elevated expression of photoreceptor-secreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.

Indexed as

3-O-MethylglucoseAcidsAnimalsCell MovementDeoxyglucoseDiabetes MellitusDiabetic RetinopathyEndothelial CellsEpendymoglial CellsEye ProteinsGlycolysisHumansIntravitreal InjectionsMice, Inbred C57BLMice, TransgenicPhotoreceptor Cells, Vertebrate3-O-MethylglucoseAcidsDeoxyglucoseEye ProteinsProtective AgentsRecombinant ProteinsRetinol-Binding ProteinsRetinol-Binding Proteins, InterstitialVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID31270273
PMCPMC7132633
OpenAlexW2953417534

What OpenQuestion holds

Textmetadata
LicenceTDM
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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.