CD34 marks angiogenic tip cells in human vascular endothelial cell cultures

The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review

Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemi

Endothelial Tip Cells in Ocular Angiogenesis: Potential Target for Anti-Angiogenesis Therapy

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. (J Histochem Cytochem 61: 101-115, 2013

Refractive outcomes after phacovitrectomy surgery

To evaluate the refractive accuracy of intraocular lens (IOL) power calculation after phacovitrectomy. Eye Hospital Zonnestraal and Department of Ophthalmology Academic Medical Center, Amsterdam, the Netherlands. Retrospective comparative case series. Refraction results 1 month after phacovitrectomy or phacoemulsification were compared with predicted refractions calculated using the IOLMaster 500 and the Haigis formula. Indications for vitrectomy were macular pucker, macular hole, vitreous floaters, vitreous hemorrhage, and vitreomacular traction. Enrolled eyes had an axial length (AL) between 20.13 mm and 29.43 mm. The phacovitrectomy group comprised 133 eyes (133 patients) and the phacoemulsification group, 132 eyes (132 patients). The refractive outcomes after phacovitrectomy (-0.06 diopter [D] ± 0.50 [SD]) and phacoemulsification (-0.08 ± 0.47 D) were comparable (P = .74). The final postoperative refraction was within ±1.00 D of the preoperative refractive target in 94.9% and 94.6% of phacovitrectomy cases and phacoemulsification cases, respectively. Subgroup analysis found no increased risk for refractive surprises after gas tamponade or in eyes with an AL of 26.00 mm or greater. Standard IOL power calculation used in regular phacoemulsification surgery was accurate in phacovitrectomy procedures in eyes with a wide range of AL and a wide range of vitrectomy indications. No tendency toward a myopic shift was found. Dr. Lapid-Gortzak is a clinical investigator for, speaker for, and consultant to Alcon Laboratories, Inc., Hanita Lenses, a speaker for Santen Pharmaceutical Co., and a consultant to Sanoculis and Orca Surgical. None of the authors has a financial or proprietary interest in any material or method mentione

Rubella virus-associated uveitis in a nonvaccinated child

PURPOSE: To report presumed Fuchs heterochromic uveitis (FHU) associated with Rubella virus (RV)-specific intraocular antibody production in a child who was not vaccinated against rubella. DESIGN: Observational case report. METHODS: We examined a 13-year-old boy with chronic anterior uveitis complicated by mature cataract. Two aqueous humor (AH) samples taken with an interval of four weeks were analyzed for intraocular antibody production against RV by calculation of the Goldmann-Witmer coefficient. RESULTS: The patient showed all the clinical signs for FHU: iris atrophy, stellate keratic precipitates, and cataract. Analysis of the AH demonstrated intraocular antibody production against RV in two sequential samples. CONCLUSIONS: The data show that RV-associated uveitis can already present during childhood. Moreover, this finding suggests that nonvaccinated children may be at risk to develop uveitis after RV infectio