ArticleExperimental eye research2019
Endogenous insulin signaling in the RPE contributes to the maintenance of rod photoreceptor function in diabetes.
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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- 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 · 2022Pooled it
- Nonlinear Associations of Estimated Glucose Disposal Rate With Incident Age-Related Eye Diseases: Implications for Metabolic Risk Stratification.Investigative ophthalmology & visual science · 2026Article
- Insulin production in the retina drives autocrine signalling and metabolism reprogramming of the ARPE-19, a retinal pigment epithelium cellular model.Cellular and molecular life sciences : CMLS · 2026Article
- Local Insulin for Local Needs? Insights into Retinal Insulin Signaling and RPE Metabolism.Biomolecules · 2025Review
- Article
- Diet, Mitochondrial Dysfunction, Vascular Endothelial Damage, and the Microbiome: Drivers of Ocular Degenerative and Inflammatory Diseases.Ophthalmology and therapy · 2025Review
- Fetuin-B Interacts With Insulin Receptor-β and Promotes Insulin Resistance in Retina Cells.Investigative ophthalmology & visual science · 2024Article
- Towards a New Biomarker for Diabetic Retinopathy: Exploring RBP3 Structure and Retinoids Binding for Functional Imaging of Eyes In Vivo.International journal of molecular sciences · 2023Review
- Phagocytosis in the retina promotes local insulin production in the eye.Nature metabolism · 2023Article
- Effect of miR-27b-3p and Nrf2 in human retinal pigment epithelial cell induced by high-glucose.International journal of ophthalmology · 2023Article
- Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy.Nature communications · 2022Article
- Autonomous regulation of retinal insulin biosynthesis in diabetes.Neuropeptides · 2022Article
- Functional Changes Within the Rod Inner Segment Ellipsoid in Wildtype Mice: An Optical Coherence Tomography and Electron Microscopy Study.Investigative ophthalmology & visual science · 2022Article
- Photoreceptor cells and RPE contribute to the development of diabetic retinopathy.Progress in retinal and eye research · 2021Review
- Quantitative analysis of retinal vessel density and thickness changes in diabetes mellitus evaluated using optical coherence tomography angiography: a cross-sectional study.BMC ophthalmology · 2021Observational
- Mitophagy, Ferritinophagy and Ferroptosis in Retinal Pigment Epithelial Cells Under High Glucose Conditions: Implications for Diabetic Retinopathy and Age-Related Retinal Diseases.JOJ ophthalmology · 2021Article
- Diabetic Retinopathy and Insulin Insufficiency: Beta Cell Replacement as a Strategy to Prevent Blindness.Frontiers in endocrinology · 2021Article
- Clinical characteristics and ultra-widefield fundus image analysis of two siblings with Bardet-Biedl syndrome type 1 p.Met390Arg variant.American journal of ophthalmology case reports · 2020Article
- Preventing diabetic retinopathy by mitigating subretinal space oxidative stressVisual neuroscience · 2020Review
- Transcriptome Analyses of lncRNAs in A2E-Stressed Retinal Epithelial Cells Unveil Advanced Links between Metabolic Impairments Related to Oxidative Stress and Retinitis Pigmentosa.Antioxidants (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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.