| Autor: |
Bosma EK; Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands., van Noorden CJF; Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia., Schlingemann RO; Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.; Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland., Klaassen I; Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. i.klaassen@amc.uva.nl.; Ocular Angiogenesis Group, Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Meibergdreef 15, Room L3-154, 1105 AZ, Amsterdam, The Netherlands. i.klaassen@amc.uva.nl. |
| Abstrakt: |
Breakdown of the blood-brain barrier (BBB) or inner blood-retinal barrier (BRB), induced by pathologically elevated levels of vascular endothelial growth factor (VEGF) or other mediators, can lead to vasogenic edema and significant clinical problems such as neuronal morbidity and mortality, or vision loss. Restoration of the barrier function with corticosteroids in the brain, or by blocking VEGF in the eye are currently the predominant treatment options for brain edema and diabetic macular edema, respectively. However, corticosteroids have side effects, and VEGF has important neuroprotective, vascular protective and wound healing functions, implying that long-term anti-VEGF therapy may also induce adverse effects. We postulate that targeting downstream effector proteins of VEGF and other mediators that are directly involved in the regulation of BBB and BRB integrity provide more attractive and safer treatment options for vasogenic cerebral edema and diabetic macular edema. The endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), a protein associated with trans-endothelial transport, emerges as candidate for this approach. PLVAP is expressed in a subset of endothelial cells throughout the body where it forms the diaphragms of caveolae, fenestrae and trans-endothelial channels. However, PLVAP expression in brain and eye barrier endothelia only occurs in pathological conditions associated with a compromised barrier function such as cancer, ischemic stroke and diabetic retinopathy. Here, we discuss the current understanding of PLVAP as a structural component of endothelial cells and regulator of vascular permeability in health and central nervous system disease. Besides providing a perspective on PLVAP identification, structure and function, and the regulatory processes involved, we also explore its potential as a novel therapeutic target for vasogenic cerebral edema and retinal macular edema. |
