RGD Reference Report - Inhibition of EGF signaling protects the diabetic retina from insulin-induced vascular leakage. - Rat Genome Database

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Inhibition of EGF signaling protects the diabetic retina from insulin-induced vascular leakage.

Authors: Sugimoto, M  Cutler, A  Shen, B  Moss, SE  Iyengar, SK  Klein, R  Folkman, J  Anand-Apte, B 
Citation: Sugimoto M, etal., Am J Pathol. 2013 Sep;183(3):987-95. doi: 10.1016/j.ajpath.2013.05.017. Epub 2013 Jul 3.
RGD ID: 10059675
Pubmed: PMID:23831329   (View Abstract at PubMed)
PMCID: PMC3763764   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajpath.2013.05.017   (Journal Full-text)

Diabetes mellitus is a disease with considerable morbidity and mortality worldwide. Breakdown of the blood-retinal barrier and leakage from the retinal vasculature leads to diabetic macular edema, an important cause of vision loss in patients with diabetes. Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes, insulin therapies for control of glucose metabolism cannot prevent long-term retinal complications. The phenomenon of temporary paradoxical worsening of diabetic macular edema after insulin treatment has been observed in a number of studies. In prospective studies on non-insulin-dependent (type 2) diabetes mellitus patients, a change in treatment from oral drugs to insulin was often associated with a significant increased risk of retinopathy progression and visual impairment. Although insulin therapies are critical for regulation of the metabolic disease, their role in the retina is controversial. In this study with diabetic mice, insulin treatment resulted in increased vascular leakage apparently mediated by betacellulin and signaling via the epidermal growth factor (EGF) receptor. In addition, treatment with EGF receptor inhibitors reduced retinal vascular leakage in diabetic mice on insulin. These findings provide unique insight into the role of insulin signaling in mediating retinal effects in diabetes and open new avenues for therapeutics to treat the retinal complications of diabetes mellitus.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetic retinopathy treatmentISOEgfr (Mus musculus)10059675; 10059675associated with Diabetes Mellitus and ExperimentalRGD 
diabetic retinopathy treatmentIMP 10059675associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)


Additional Information