Evidence mapPaperPMID 30543793Full record

ArticleExperimental eye research2019

Endogenous insulin signaling in the RPE contributes to the maintenance of rod photoreceptor function in diabetes.

Matthew J Tarchick, Alecia H Cutler, Timothy D Trobenter, Michael R Kozlowski, Emily R Makowski, Nicholas Holoman, Jianning Shao, Bailey Shen, Bela Anand-Apte, Ivy S Samuels

Abstract read
In one paragraph

Article in Experimental eye research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Structure-Function Relationships in the Rodent Streptozotocin-Induced Model for Diabetic Retinopathy: A Systematic Review.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2022
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Observational
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Matthew J TarchickResearch Service, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Alecia H CutlerDepartment of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Timothy D TrobenterResearch Service, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Michael R KozlowskiDepartment of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Emily R MakowskiResearch Service, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Nicholas HolomanResearch Service, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Jianning ShaoCleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland Clinic Foundation, Cleveland, OH, USA.
Bailey ShenDepartment of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Bela Anand-ApteDepartment of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Ivy S SamuelsResearch Service, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Electronic address: Ivy.Samuels@va.gov.
Cleveland Clinic · USCleveland Clinic Lerner College of Medicine · US

Funding

NEI Center Core Grant for Vision ResearchP30EY025585 · CLEVELAND CLINIC LERNER COM-CWRU · 2025 to 2025
$644k
BLRD VA I01 BX002754NEI NIH HHS P30 EY025585NEI NIH HHS R01 EY020861NEI NIH HHS R01 EY026181NEI NIH HHS R01 EY027083
6 · The paper itself

Abstract

In diabetes, there are two major physiological aberrations: (i) Loss of insulin signaling due to absence of insulin (type 1 diabetes) or insulin resistance (type 2 diabetes) and (ii) increased blood glucose levels. The retina has a high proclivity to damage following diabetes, and much of the pathology seen in diabetic retinopathy has been ascribed to hyperglycemia and downstream cascades activated by increased blood glucose. However, less attention has been focused on the direct role of insulin on retinal physiology, likely due to the fact that uptake of glucose in retinal cells is not insulin-dependent. The retinal pigment epithelium (RPE) is instrumental in maintaining the structural and functional integrity of the retina. Recent studies have suggested that RPE dysfunction is a precursor of, and contributes to, the development of diabetic retinopathy. To evaluate the role of insulin on RPE cell function directly, we generated a RPE specific insulin receptor (IR) knockout (RPEIRKO) mouse using the Cre-loxP system. Using this mouse, we sought to determine the impact of insulin-mediated signaling in the RPE on retinal function under physiological control conditions as well as in streptozotocin (STZ)-induced diabetes. We demonstrate that loss of RPE-specific IR expression resulted in lower a- and b-wave electroretinogram amplitudes in diabetic mice as compared to diabetic mice that expressed IR on the RPE. Interestingly, RPEIRKO mice did not exhibit significant differences in the amplitude of the RPE-dependent electroretinogram c-wave as compared to diabetic controls. However, loss of IR-mediated signaling in the RPE reduced levels of reactive oxygen species and the expression of pro-inflammatory cytokines in the retina of diabetic mice. These results imply that IR-mediated signaling in the RPE regulates photoreceptor function and may play a role in the generation of oxidative stress and inflammation in the retina in diabetes.

Indexed as

AnimalsBlood GlucoseBlotting, WesternDiabetes Mellitus, ExperimentalDiabetic RetinopathyElectroretinographyGenetic MarkersInsulinMaleMiceMice, Inbred C57BLMice, KnockoutOxidative StressReactive Oxygen SpeciesReal-Time Polymerase Chain ReactionReceptor, InsulinBlood GlucoseGenetic MarkersInsulinReactive Oxygen SpeciesReceptor, InsulinDiabetic retinopathyInsulinOxidative stressPhotoreceptorRetinal pigment epithelium

Identifiers

PMID30543793
PMCPMC6389378
OpenAlexW2905173078

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.