cellular signaling and potential new treatment targets in diabetic retinopathy细胞信号和潜在的新的治疗糖尿病性视网膜病变的目标.pdfVIP

Hindawi Publishing Corporation Experimental Diabetes Research Volume 2007, Article ID 31867, 12 pages doi:10.1155/2007/31867 Review Article Cellular Signaling and Potential New Treatment Targets in Diabetic Retinopathy Zia A. Khan and Subrata Chakrabarti Received 28 December 2006; Revised 2 May 2007; Accepted 13 September 2007 Recommended by Timothy Kern Dysfunction and death of microvascular cells and imbalance between the production and the degradation of extracellular matrix (ECM) proteins are a characteristic feature of diabetic retinopathy (DR). Glucose-induced biochemical alterations in the vascu- lar endothelial cells may activate a cascade of signaling pathways leading to increased production of ECM proteins and cellular dysfunction/death. Chronic diabetes leads to the activation of a number of signaling proteins including protein kinase C, pro- tein kinase B, and mitogen-activated protein kinases. These signaling cascades are activated in response to hyperglycemia-induced oxidative stress, polyol pathway, and advanced glycation end product formation among others. The aberrant signaling pathways ultimately lead to activation of transcription factors such as nuclear factor-κB and activating protein-1. The activity of these tran- scription factors is also regulated by epigenetic mechanisms through transcriptional coactivator p300. These complex signaling pathways may be involved in glucose-induced alterations of endothelial cell phenotype leading to the production of increased ECM proteins and vasoactive effector molecules causing functional and structural changes in the microvasculature. Understand- ing of such mechanistic pathways will help to develop future adjuvant therapies for diabetic retinopathy. Copyright © 2007 Z. A. Khan and S. Chakrabarti. This is an open