Retinal vascular recovery revealed by retinal imaging following neonatal hypoxia ischemia in mice: Is there a role for tyrosine kinase receptor modulation?

Objective: Hypoxic ischemic encephalopathy (HIE) secondary to perinatal asphyxia leads to long-term visual disabilities. Dilated retinal exams in human newborns with HIE is an emerging diagnostic tool, but phenotypes of hypoxia ischemia (HI) related retinal vascular injury are unclear. 7,8-Dihydroxyflavone (7,8-DHF) is a TrkB agonist with protective effects on HI-related brain damage.

Role of the Endothelium in Neonatal Diseases.

In both fetal and neonatal physiologic and pathologic processes in most organs, endothelial cells are known to play critical roles. Although the endothelium is one of the most ubiquitous cell type in the body, the tight adherence to the blood vessel wall has made it difficult to study their diverse function and structure. In this article, we have reviewed endothelial cell origins and explored their heterogeneity in terms of structure, function, developmental changes, and their role in inflammatory and infectious diseases.

Retinopathy of prematurity shows alterations in Vegfa isoform expression.

Background: Pathologic ocular neovascularization in retinopathy of prematurity (ROP) and other proliferative retinopathies are characterized by dysregulation of vascular endothelial growth factor-A (VEGF-A). A study of Vegfa isoform expression during oxygen-induced ischemic retinopathy (OIR) may enhance our understanding of Vegf dysregulation.

Methods: Following induction of OIR, immunohistochemistry and polymerase chain reaction (PCR) was performed on room air (RA) and OIR mice.

Role of macrophages in fetal development and perinatal disorders.

In the fetus and the neonate, altered macrophage function has been implicated not only in inflammatory disorders but also in developmental abnormalities marked by altered onset, interruption, or imbalance of key structural changes. The developmental role of macrophages were first noted nearly a century ago, at about the same time when these cells were being identified as central effectors in phagocytosis and elimination of microbes. Since that time, we have made considerable progress in understanding the diverse roles that these cells play in both physiology and disease.

The role of integrins in inflammation and angiogenesis.

Integrins are heterodimeric transmembrane cell adhesion molecules made up of alpha (α) and beta (β) subunits arranged in numerous dimeric pairings. These complexes have varying affinities to extracellular ligands. Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis.

Long-term evaluation of retinal morphology and function in a mouse model of oxygen-induced retinopathy.

Purpose: Retinopathy of prematurity (ROP) is a condition of aberrant retinal vascularization in premature infants in response to high levels of oxygen used for critical care that can potentially cause blindness. Although therapies to mitigate vascular abnormalities are being evaluated, functional deficits often remain in patients with treated or regressed ROP. This study investigated long-term outcomes of hyperoxia on retinal morphology and function using a mouse model of oxygen-induced ischemic retinopathy (OIR).

Longer Breastfeeding Associated with Childhood Anemia in Rural South-Eastern Nigeria.

Introduction: Child mortality rate in sub-Saharan Africa is 29 times higher than that in industrialized countries. Anemia is one of the preventable causes of child morbidity. During a humanitarian medical mission in rural South-Eastern Nigeria, the prevalence and risk factors of anemia were determined in the region in order to identify strategies for reduction.

rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.

Objective: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants.

Study Design: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 23 weeks to 27 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 29 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 40 weeks.

Intravitreal Delivery of VEGF-A-loaded PLGA Microparticles Reduces Retinal Vaso-Obliteration in an In Vivo Mouse Model of Retinopathy of Prematurity.

Purpose: Retinopathy of prematurity (ROP) is a condition of abnormal retinal vascularization with reduced levels of vascular endothelial growth factor (VEGF) causing vaso-obliteration (Phase I), followed by abnormal neovascularization from increased VEGF (Phase II). We hypothesized that intravitreal pro-angiogenic VEGF-A in microparticle form would promote earlier retinal revascularization in an oxygen-induced ischemic retinopathy (OIR) mouse model.

Materials And Methods: Wildtype mice (39) were exposed to 77% oxygen from postnatal day 7 (P7) to P12.

Simultaneous assessment of aberrant retinal vascularization, thickness, and function in an in vivo mouse oxygen-induced retinopathy model.

Background: Retinopathy of prematurity is a condition of abnormal retinal vascularization in premature infants. The effect of abnormal vascularization on retinal structure and function is unclear. In vivo studies of retinal vascularization, thickness, and function were performed in mice with oxygen-induced retinopathy (OIR mice).

Simultaneous Fluorescein Angiography and Spectral Domain Optical Coherence Tomography Correlate Retinal Thickness Changes to Vascular Abnormalities in an In Vivo Mouse Model of Retinopathy of Prematurity.

Background: Retinopathy of prematurity (ROP) is a condition of abnormal retinal vascular development (RVD) in premature infants. Fluorescein angiography (FA) has depicted phases (early, mid, late, and mature) of RVD in oxygen-induced retinopathy (OIR) mice. We sought to establish the relationship between retinal structural and vascular changes using simultaneous FA and spectral domain optical coherence tomography (SD-OCT).

In Vivo Angiography Quantifies Oxygen-Induced Retinopathy Vascular Recovery.

Purpose: Retinopathy of prematurity (ROP) is a potentially blinding vasoproliferative disease. There is no standardized way to quantify plus disease (tortuous and dilated retinal vessels) or characterize abnormal recovery during ROP monitoring. This study objectively studies vascular features in live mice during development using noninvasive retinal imaging.

Correspondence of retinal thinning and vasculopathy in mice with oxygen-induced retinopathy.

The aberrantly vascularized peripheral retina in retinopathy of prematurity (ROP) may be associated with visual field constriction, retinal dysfunction, and abnormalities in retinal thickness which is commonly assessed by spectral domain optical coherence tomography (SDOCT). However, due to the limitation of SDOCT for peripheral retinal imaging, retinal thickness in avascular peripheral retina in ROP has not been evaluated. Oxygen induced retinopathy (OIR) in mice has features of vasculopathy similar to those in human ROP.

In vivo retinal vascular oxygen tension imaging and fluorescein angiography in the mouse model of oxygen-induced retinopathy.

Purpose: Oxygenation abnormalities are implicated in the development of retinopathy of prematurity (ROP). The purpose of this study is to report in vivo retinal vascular oxygen tension (PO2) measurements and fluorescein angiography (FA) findings in the mouse model of oxygen-induced retinopathy (OIR).

Methods: We exposed 19 neonatal mice to 77% oxygen from postnatal day 7 (P7) to P12 (OIR), while 11 neonatal mice were kept under room air (control).

Patent ductus arteriosus in premature neonates.

Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a haemodynamically significant patent ductus arteriosus (PDA) can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation and increase the risk of bronchopulmonary dysplasia, intraventricular haemorrhage, renal dysfunction, cerebral palsy and mortality. We review the pathophysiology, clinical features and assessment of haemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity.