Ocular angiogenesis: mechanisms and recent advances in therapy.
Ocular angiogenesis, the formation of new blood vessels from the existing vascular tree, is an important cause for severe loss of vision. It can occur in a spectrum of ocular disorders such as age-related macular degeneration (AMD), diabetic retinopathy, retinal artery or vein occlusion, and retinopathy of prematurity (ROP). One of the underlying causes of vision loss in proliferative retinal diseases is the increased vascular permeability leading to retinal edema, vascular fragility resulting in hemorrhage, or fibrovascular proliferation with tractional and rhegmatogenous retinal detachment. Pro- and antiangiogenic factors regulate an "angiogenic switch," which when turned on, leads to the pathogenesis of the above ocular diseases. Although neovascularization tends to occur at a relatively late stage in the course of many ocular disorders, it is an attractive target for therapeutic intervention, since it represents a final common pathway in processes that are multifactorial in etiology and is the event that typically leads directly to visual loss. Identification of these angiogenesis regulators has enabled the development of novel therapeutic approaches. In this light, antibodies directed against common markers of neovasculature, expressed in different diseases, may open up a very general and widely applicable approach for diagnostic and therapeutic interventions. Local gene transfer, that is, the intraocular delivery of recombinant viruses carrying genes encoding angiostatic proteins and small interfering RNA (siRNA) against vascular endothelial growth factor (VEGF) and VEGF receptors, offers the possibility of targeted, sustained, and regulatable delivery of angiostatic proteins and other angiogenic regulators to the retina. Recent progress has enabled the planning of clinical trials of gene therapy for ocular neovascularization.
Rajappa
Medha
M
Department of Ocular Biochemistry, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Saxena
Parul
P
Kaur
Jasbir
J
D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000628:therapy*; D012164:Retinal Diseases / Q000628:therapy*