Release of experimental retinal vein occlusions by direct intraluminal injection of ocriplasmin

Ophthalmic researc

Robotic Assisted Cannulation of Occluded Retinal Veins

Ophthalmic researc

Vascular endothelial growth factor receptor 1 expression in nasal polyp tissue

Background: Edema represents a key feature of nasal polyp (NP) disease. Members of the vascular endothelial growth factor (VEGF) family may be involved, but the precise role of VEGF-A, VEGF-B, placental growth factor (PlGF), and their receptors VEGFR1 and VEGFR2 in NP edema formation remains elusive. Objective: Exploring the expression of VEGF family members and their receptors and their correlation with clinical, radiological, and edema markers in NP. Methods: The expression of VEGF-A, VEGF-B, PlGF, VEGFR1, and VEGFR2 was measured in NP (n=23) and control tissue (n=22) at mRNA and protein level. Edema was evaluated by measuring albumin levels and wet/dry ratios. Computed tomography (CT) scans were scored using the Lund-Mackay scoring system. IL-5 mRNA expression was determined by real-time RT-PCR. Cell suspensions from NP (n=10) and control tissue (n=12) were stimulated in vitro with IL-1 or TNF. Results: mRNA expression of VEGFR1 and VEGF-B was significantly higher in NP compared with control tissue. Expression levels of VEGF-B and VEGFR1 significantly correlated with NP albumin content (VEGF-B: P=0.0208; VEGFR1: P=0.0293), CT scan scores (VEGF-B: P=0.0075; VEGFR1: P=0.0068), and IL-5 mRNA (VEGF-B: P=0.0027; VEGFR1: P=0.0001). In vitro stimulation of control and NP tissue cell suspensions with IL-1 or TNF significantly reduced the expression of VEGFR2 in control tissue, without altering VEGFR1 and VEGF-B expression. hVEGF-B induced nitric oxide production in NP macrophages (P<0.05). Conclusion: Expression levels of VEGFR1 and VEGF-B correlate with edema and clinical markers of NP disease and therefore represent potential therapeutic targets

Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization.

A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2(+/-) mice. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation and inhibited tumor cell invasion, intravasation, and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent cell type, lacking filopodia and arrayed in a phalanx formation. This transition relied on HIF-driven upregulation of (soluble) VEGFR-1 and VE-cadherin. Thus, decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial cells to readjust their shape and phenotype to restore oxygen supply. Inhibition of PHD2 may offer alternative therapeutic opportunities for anticancer therapy