Ocular neovascularisation and excessive vascular permeability.
Diseases complicated by vascular leakage and/or neovascularisation in the eye are responsible for the vast majority of visual morbidity and blindness in developed countries. The molecular signals that control vascular permeability and neovascularisation in the eye are being defined. Members of the vascular endothelial growth factor (VEGF) family are key stimulators that interact with two tyrosine kinase receptors, VEGF receptor (VEGFR)1 and 2; binding to two other receptors that lack tyrosine kinase activity, the neuropilins, is also important. Signalling through the VEGF pathway is modulated by the Tie2 receptor and its binding partners, the angiopoietins. Each of the participants in these two signalling pathways provides a potential target for intervention. Several proteins with antiangiogenic activity balance the stimulators and the outcome is determined by the net balance. Endostatin suppresses vascular permeability as well as ocular neovascularisation, suggesting that vascular leakage may also be regulated by counteracting proteins. Gene transfer provides a useful way to influence these balances. Clinical trials are underway to test whether these mechanisms can be translated into new therapies.
Campochiaro
Peter A
PA
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Maumenee 719, 600 N. Wolfe Street, Baltimore, MD 21287-9277, USA. pcampo@jhmi.edu
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042682:Angiopoietins / Q000502:physiology; D043168:Angiostatins / Q000502:physiology; D002199:Capillary Permeability; D002986:Clinical Trials as Topic; D016510:Corneal Neovascularization / Q000503:physiopathology* / Q000628:therapy; D003930:Diabetic Retinopathy / Q000503:physiopathology / Q000628:therapy; D016503:Drug Delivery Systems; D043169:Endostatins / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005136:Eye Proteins / Q000502:physiology / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008269:Macular Edema / Q000503:physiopathology* / Q000628:therapy; D009414:Nerve Growth Factors / Q000502:physiology / Q000627:therapeutic use; D039921:Neuropilins / Q000502:physiology; D011244:Pregnadienediols / Q000627:therapeutic use; D042787:Receptor, TIE-2 / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D015843:Serpins / Q000502:physiology / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D042682:Angiopoietins; D043168:Angiostatins; D043169:Endostatins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D039921:Neuropilins; D011244:Pregnadienediols; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor; D015843:Serpins; D019717:Tissue Inhibitor of Metalloproteinase-3; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C418047:anecortave acetate