TY - JOUR
T1 - Vascular endothelial growth factor and diabetic retinopathy
T2 - Pathophysiological mechanisms and treatment perspectives
AU - Caldwell, Ruth B.
AU - Bartoli, Manuela
AU - Behzadian, M. Ali
AU - El-Remessy, Azza E.B.
AU - Al-Shabrawey, Mohamed
AU - Platt, Daniel H.
AU - Caldwell, R. William
PY - 2003/11
Y1 - 2003/11
N2 - Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes. Therefore, VEGF represents an exciting target for therapeutic intervention in diabetic retinopathy. This review highlights the current understanding of the mechanisms that regulate VEGF gene expression and mediate its biological effects and how these processes may become altered during diabetes. The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction. Finally, potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are considered.
AB - Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes. Therefore, VEGF represents an exciting target for therapeutic intervention in diabetic retinopathy. This review highlights the current understanding of the mechanisms that regulate VEGF gene expression and mediate its biological effects and how these processes may become altered during diabetes. The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction. Finally, potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are considered.
KW - Angiogenesis
KW - Diabetic retinopathy
KW - Reactive oxygen species
KW - Retina
KW - Vascular endothelial growth factor
KW - Vascular permeability
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U2 - 10.1002/dmrr.415
DO - 10.1002/dmrr.415
M3 - Review article
C2 - 14648803
AN - SCOPUS:0346777254
SN - 1520-7552
VL - 19
SP - 442
EP - 455
JO - Diabetes/Metabolism Research and Reviews
JF - Diabetes/Metabolism Research and Reviews
IS - 6
ER -