Abstract
Vasculogenesis and angiogenesis play a crucial role in embryonic development. Pathological neovascularization in ocular tissues can lead to vision-threatening vascular diseases, including proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, choroidal neovascularization, and corneal neovascularization. Neovascularization involves various cellular processes and signaling pathways and is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF). Modulating these circuits may represent a promising strategy to treat ocular neovascular diseases. Lipid mediators derived from membrane lipids are abundantly present in most tissues and exert a wide range of biological functions by regulating various signaling pathways. In particular, glycerophospholipids, sphingolipids, and polyunsaturated fatty acids exert potent pro-angiogenic or anti-angiogenic effects, according to the findings of numerous preclinical and clinical studies. In this review, we summarize the current knowledge regarding the regulation of ocular neovascularization by lipid mediators and their metabolites. A better understanding of the effects of lipid signaling in neovascularization may provide novel therapeutic strategies to treat ocular neovascular diseases and other human disorders.
Highlights
Living organisms are composed of various organic compounds, including proteins, carbohydrates, nucleic acids, and lipids
Angiogenesis is the formation of new vessels in response to angiogenic factors; the new vessels are formed by sprouting of endothelial cells in pre-existing vessels [14]
Gα12/Gα13-Rho-ROCK pathway activation inhibited delta-like ligand 4 (DLL4)/Notch signaling by activating Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in endothelial cells at the vascular front
Summary
Living organisms are composed of various organic compounds, including proteins, carbohydrates, nucleic acids, and lipids. Angiogenesis is the formation of new vessels in response to angiogenic factors; the new vessels are formed by sprouting of endothelial cells in pre-existing vessels [14]. Chronic hypoxia induces the production of angiogenic factors in human tissues, promoting vascular growth from pre-existing vessels [17]. Pre-retinal neovascularization can lead to vision loss. Intravitreal injection of VEGF-targeting agents is currently a standard treatment option for patients with visual impairments due to pathologic retinal neovascularization [38,39]. Under pathological conditions, including corneal infection, traumatic injury, ocular surface inflammation, and limbal stem cell deficiency, corneal neovascularization and sprouting from the pericorneal plexus can occur [45,46,47], potentially leading to vision loss. We summarize current knowledge regarding the role of lipid signaling in ocular neovascularization
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