1. Endothelial tip cells in ocular angiogenesis : potential target for anti-angiogenesis therapyMartin J. Siemerink, Ingeborg Klaassen, Cornelis J. F. van Noorden, Reinier O. Schlingemann, 2013, izvirni znanstveni članek Povzetek: Endothelial tip cells are leading cells at the tips of vascular sprouts coordinating multiple processes during angiogenesis. In the developing retina, tip cells play a tightly controlled, timely role in angiogenesis. In contrast, excessive numbers of tip cells are a characteristic of the chaotic pathological blood vessels in proliferative retinopathies. Tip cells control adjacent endothelial cells in a hierarchical manner to form the stalk of the sprouting vessel, using, among others, the VEGF-DLL-Notch signaling pathway, and recruit pericytes. Tip cells are guided toward avascular areas by signals from the local extracellular matrix that are released by cells from the neuroretina such as astrocytes. Recently, tip cells were identified in endothelial cell cultures, enabling identification of novel molecular markers and mechanisms involved in tip cell biology. These mechanisms are relevant for understanding proliferative retinopathies. Agents that primarily target tip cells can block pathological angiogenesis in the retina efficiently and safely without adverse effects. A striking example is platelet-derived growth factor, which was recently shown to be an efficacious additional target in the treatment of retinal neovascularization. Here we discuss these and other tip cell-based strategies with respect to their potential to treat patients with ocular diseases dominated by neovascularization.
Ključne besede: angiogenesis, endothelial tip cell, proliferative retinopathy, anti-angiogenesis therapy, retinal neovascularization, vascular sprouts, endothelial stalk cell, molecular mediators of angiogenesis, pericytes
Objavljeno v DiRROS: 02.08.2024; Ogledov: 148; Prenosov: 87
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2. Spatial and temporal recruitment of the neurovascular unit during development of the mouse blood-retinal barrierAnne-Eva van der Wijk, Ilse M.C. Vogels, Henk A. van Veen, Cornelis J. F. van Noorden, Reinier O. Schlingemann, Ingeborg Klaassen, 2018, izvirni znanstveni članek Povzetek: The inner blood-retinal barrier (BRB) is made up by the neurovascular unit, consisting of endothelial cells, pericytes and glial cells. The BRB maintains homeostasis of the neural retina, but in pathological eye conditions the neurovascular unit is often disrupted, causing BRB loss. Here, we investigated in detail temporal and spatial recruitment of the neurovascular unit in the neonatal mouse retina from postnatal day (P)3 to P25 employing immunohistochemical staining of vascular endothelium (isolectin B4), pericytes (α-SMA and NG2) and astrocytes (GFAP). In addition, we investigated gene expression of polarized astrocytic end-feet markers aquaporin-4 and laminin α2 chain with qPCR. We observed GFAP-positive cells migrating ahead of the retinal vasculature during the first postnatal week, suggesting that the retinal vasculature follows an astrocytic meshwork. From P9 onwards, astrocytes acquired a mature phenotype, with a more stellate shape and increased expression of aquaporin-4. NG2-positive cells and tip cells co-localized at P5 and invaded the retina together as a vascular sprouting front. In summary, these data suggest that recruitment of the cell types of the neurovascular unit is a prerequisite for proper retinal vascularization and BRB formation.
Ključne besede: endothelial cells, astrocytes, pericytes, retinal development
Objavljeno v DiRROS: 24.07.2024; Ogledov: 131; Prenosov: 117
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3. New insights in ATP synthesis as therapeutic target in cancer and angiogenic ocular diseasesCornelis J. F. van Noorden, Bahar Yetkin-Arik, Paola Serrano Martinez, Noëlle Bakker, Mathilda E. van Breest Smallenburg, Reinier O. Schlingemann, Ingeborg Klaassen, Bernarda Majc, Anamarija Habič, Urban Bogataj, Katrin S. Galun, Miloš Vittori, Mateja Erdani-Kreft, Metka Novak, Barbara Breznik, Vashendriya V. V. Hira, 2024, pregledni znanstveni članek Povzetek: Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production.
Ključne besede: aerobic glycolysis, anaerobic glycolysis, angiogenesis, ATP synthesis, cancer cells, cancer stem cells, endothelial cells, energy metabolism, eye diseases, oxidative phosphorylation, pericytes, retina, Warburg effect
Objavljeno v DiRROS: 18.06.2024; Ogledov: 201; Prenosov: 125
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