Hypoxia-induced responses by endothelial colony-forming cells are modulated by placental growth factor

BACKGROUND: Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined. METHODS: In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen. We defined the response of ECFCs to 1% O(2) exposure at acute and chronic time points. RESULTS: In response to low oxygen, changes in ECFC cell shape, proliferation, size and cytoskeleton phenotype were detected. An increase in the number of senescent ECFCs also occurred as a result of long-term culture in 1% O(2). Low oxygen exposure altered ECFC migration and tube formation in Matrigel®. Increases in angiogenic factors secreted from ECFCs exposed to hypoxia were also detected, in particular, after treatment with placental growth factor (PlGF). Exposure of cells to agents that stabilise hypoxia-inducible factors such as dimethyloxalylglycine (DMOG) also increased PlGF levels. Conditioned medium from both hypoxia-treated and DMOG-treated cells inhibited ECFC tube formation. This effect was reversed by the addition of PlGF neutralising antibody to the conditioned medium, confirming the direct role of PlGF in this effect. CONCLUSIONS: This study deepens our understanding of the response of ECFCs to hypoxia and also identifies a novel and important role for PlGF in regulating the vasculogenic potential of ECFCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0430-0) contains supplementary material, which is available to authorized users

Supporting positive patient experiences for rare disease care during disruptive times: findings from a multicentre study

Introduction: We describe the perceptions and experiences of health care services during the COVID-19 pandemic of those newly diagnosed with a rare, chronic inflammatory eye disorder. Methods: We undertook a cross-sectional study nested within a longitudinal multi-centre inception cohort study. Participants were families and young people (aged under 18 years) newly diagnosed with childhood uveitis. Using a validated tool, the Health Foundation COVID-19 Survey, we captured qualitative and quantitative data. Quantitative data were analysed using descriptive summary statistics. Qualitative, free text responses were analysed using content and thematic analysis. Results: Responses received from 60 families between 1st September 2020 and 30th March 2022 were analysed. Despite two in five reporting challenges in accessing medication, the majority felt comfortable accessing healthcare services (8%, 95% CI 3 - 18%, of participants expressed discomfort, versus 28%, 95% CI 26 – 28% of general population). Thematic analysis identified five themes: the value of protected spaces to safely access care; the positive role of digital health tools the experience of immature telemedicine; disintegration of care; and dealing with uncertainty. Discussion: Our findings suggest that families of children with a rare chronic condition had greater confidence in accessing healthcare during the pandemic than the general population. Nevertheless, to ensure more robust health services for such populations in future times of disruption, developments in telemedicine should be directly informed by the experiences of those with rare disease. The development of new healthcare processes which ensure the whole healthcare team has adequate information to support families should be prioritised

Long term refractive and biometric outcomes following diode laser therapy for retinopathy of prematurity

To assess the long-term refractive and biometric outcomes of diode laser-treated eyes in threshold retinopathy of prematurity (ROP). Cycloplegic autorefraction and biometry were performed, at a mean follow-up of 11 years, on 16 laser-treated eyes with threshold ROP and 9 comparison eyes with subthreshold untreated ROP. The laser treated eyes had a mean spherical equivalent of - 2.33 D with a mean astigmatic error of 1.38D. The comparison eyes had a mean spherical equivalent of +1.07 D with a mean astigmatic error of 0.42D. This trend toward increaded myopia in treated eyes did not achieve statistical significance. The myopia in the laser group appeared to be slowly progressive in nature when compared with earlier refractive data for these patients. The laser treated eyes had reduced anterior chamber depth (ACD) compared with the subthreshold eyes

RetCam image analysis of optic disc morphology in premature infants and its relation to ischaemic brain injury

To assess optic disc characteristics in premature infants with and without ischaemic brain injury and to evaluate the role of optic disc morphology in dating the injury. RetCam fundal images, cranial untrasounds and magnetic resonance imaging (MR) of 109 premature infants were analysed. The study cohort was divided into subgroups depending on the presence or absence of periventricular leucomalacia (PVL) and intraventricular haemorrhage (IVH). The control group consisted of infants with normal neuroimaging at term and 2 years of age. Using the image analysis software of the RetCam, optic disc diameter (ODD), and optic cup area (OCA)were measured at 33-34 weeks gestational age. As serial cranial ultrasonography had been performed, it was possible to date the brain injury in those infants with periventricular white matter (PVWM) damage

Case report: a case of diffuse unilateral subacute neuroretinitis (DUSN) in a child

Abstract Background Diffuse unilateral subacute neuroretinitis (DUSN) is a rare cause of posterior uveitis in the United Kingdom. It typically presents unilaterally in children and young adults but rarely bilateral cases have been reported. It is also rare to have multiple worms in the same eye causing the clinical picture. In this article, we present a challenging case of DUSN in a young girl unresponsive to conventional treatments suggesting the possibility of multiple worms being present in the same eye. Case Presentation An 8-year-old girl presented with a 2-month history of headaches. On occasions the headaches were associated with redness and watering of her left eye. She denied any visual loss or visual symptoms. Her visual acuity was reduced to 6/30 in her left eye. Fundal examination revealed a unilateral chorioretinitis. Investigation did not reveal a specific cause for the chorioretinitis. Over 15 months her visual acuity improved to 6/9 but the fundal appearance changed and a diagnosis of DUSN was made. She was treated with focal laser, systemic anti-helminthic and immunosuppressive treatments but continued to develop new, active areas of chorioretinitis, raising the possibility of multiple worms in the sub-retinal space. There is also a concern as to other central nervous system (CNS) involvement given her significant and ongoing headaches. Conclusion We present a challenging case of DUSN in a young girl; a condition that remains rare in the UK. She was unresponsive to both focal laser and systemic anti-helminthic and immunosuppressive treatments suggesting the possibility of multiple worms being present in the sub-retinal space. This case highlights the difficulties often encountered in the treatment of DUSN, even when a worm can be identified. Her visual prognosis is poor as there was ongoing recurrence of active chorioretinitis