Anti-angiogenic therapy of proliferative diabetic retinopathy.
Proliferative diabetic retinopathy (PDR) remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop this complication. The hallmark of PDR is neovascularisation (NV), abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed at preventing NV, as an adjunct to laser treatment, or as an alternative to laser treatment, would be a welcome addition to the armamentarium. PDR could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C (PKC) inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor (VEGF), insulin like growth factor-1) blockade, integrin (e.g., alpha-v beta-3) blockade or extracellular matrix alteration (e.g., with steroid compounds), or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase pathway proteins). Numerous potentially useful anti-angiogenic compounds are in development, but two drugs are presently in clinical trials for the treatment of the preproliferative stage of PDR.
Danis
R P
RP
Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA. rdanis@iupui.edu
Ciulla
T A
TA
Criswell
M
M
Pratt
L
L
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors; D053685:Laser Therapy; D008222:Lymphokines / Q000037:antagonists & inhibitors; D008866:Microsurgery; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D001786:Blood Glucose; D016228:Endothelial Growth Factors; D017127:Glycation End Products, Advanced; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007334:Insulin-Like Growth Factor I; D000449:Aldehyde Reductase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases