Abstract
In recent years, the number of patients with age-related macular degeneration (AMD) is increasing worldwide along with increased life expectancy. Currently, the standard treatment for wet-AMD is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. The upstream of VEGF is hypoxia-inducible factor (HIF), a master regulator of hypoxia-responsive genes responsive to acute and chronic hypoxia. HIF activation induces various pathological pro-angiogenic gene expressions including VEGF under retinal hypoxia, ultimately leading to the development of ocular ischemic neovascular diseases. In this regard, HIF is considered as a promising therapeutic target in ocular ischemic diseases. In clinical ophthalmology, abnormal hypofluorescent areas have been detected in the late-phase of indocyanine green angiography, which are thought to be lipid deposits at the level of Bruch’s membrane to choriocapillaris in vitreoretinal diseases. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium, and that HIF/VEGF is highly suspected to be expressed in the hypoxic retinal pigment epithelium, leading to neovascularization. In this review, we comprehensively summarize pathophysiology of AMD-related ocular diseases with the HIF/VEGF pathway from basic and clinic researches with recent findings.
Highlights
Most living things on earth use oxygen to carry out their life activities
Bruch’s membrane to choriocapillaris [9]. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium (RPE), and it is strongly suspected that hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) is expressed in hypoxic RPE, leading to the formation of neovascularization
The underlying causes of choroidal neovascularization (CNV) are complex and multifactorial [10], this review provides a comprehensive description of the pathogenesis of age-related macular degeneration (AMD)-related ocular diseases involving the HIF/VEGF pathway, including the latest findings from basic and clinical studies
Summary
Most living things on earth use oxygen to carry out their life activities. Animals have two major systems that supply oxygen systemically. It was later discovered that HIF is a master regulator of hypoxia response, controlling erythropoietin and hundreds of genes involved in angiogenesis and metabolic conversion, such as vascular endothelial growth factor (VEGF) [3]. The underlying causes of choroidal neovascularization (CNV) are complex and multifactorial [10], this review provides a comprehensive description of the pathogenesis of AMD-related ocular diseases involving the HIF/VEGF pathway, including the latest findings from basic and clinical studies. Stabilization of HIF-αs occurs, and stabilized HIF-αs go into nucleus, dimerizes with HIF-1β, and activates hypoxia-responsive gene expressions including VEGF, PDK1, BNIP3, EPO, GLUT-1, and CA9. HIF-αs stands for different forms or multiple α subunits
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