Role of IGF-1 signaling in the pathology of diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a common eye disease caused by diabetic mellitus and can lead to blindness of eye. Currently, researches on the mechanisms and clinical interventions of DR are at an early stage. Under the condition of DR, insulin is usually used for the control of blood glucose. Similar to insulin, Insulin-like growth factor-1 (IGF-1), a protein which has been reported to lower the level of blood glucose, may also promote cell survival and proliferation in various tissues. However, effects of IGF-1 on DR are complex and controversial. The effect of IGF-1 on the normalization of blood glucose is beneficial for the patients, especially those with severe insulin resistance. However, IGF-1 mediates a strong mitogenic signaling and long term application of IGF-1 may aggravate retinal deterioration through promoting the proliferation of retinal endothelial cells. IGF-1 enhances the expression of vascular endothelial growth factor and erythropoietin. The binding of IGF-I to IGF-IR also promotes the activation of multiple signaling pathways, including phosphatidylinositol 3-kinase/protein kinase B pathway, mitogen activated protein kinase pathway and nuclear factor-κB signaling pathway. All of these have been shown to be associated with the pathology of DR. In this review, we discuss the signaling pathway of IGF-1, evidence for a functional relationship between the IGF-I and DR, as well as a possible role of IGF-1 signaling pathway in the process of DR.