In some situations, cell death in the nervous system is controlled by an interplay between survival factors and negative survival signals that actively induce apoptosis. The present work indicates that the survival of Schwann cells is regulated by such a dual mechanism involving the negative survival signal transforming growth factor beta (TGFbeta), a family of growth factors that is present in the Schwann cells themselves. We analyze the interactions between this putative autocrine death signal and previously defined paracrine and autocrine survival signals and show that expression of a dominant negative c-Jun inhibits TGFbeta-induced apoptosis. This and other findings pinpoint activation of c-Jun as a key downstream event in TGFbeta-induced Schwann cell death. The ability of TGFbeta to kill Schwann cells, like normal Schwann cell death in vivo, is under a strong developmental regulation, and we show that the decreasing ability of TGFbeta to kill older cells is attributable to a decreasing ability of TGFbeta to phosphorylate c-Jun in more differentiated cells.

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Background The WHO's Vision 2020 global initiative against blindness, launched in 2000, prioritises children. Progress has been hampered by the global paucity of epidemiological data about childhood visual disability. The British Childhood Visual Impairment and Blindness Study 2 (BCVIS2) was undertaken to address this evidence gap. Methods UK-wide prospective population-based observational study of all those aged under 18 years newly diagnosed with visual impairment or blindness between Oct 1, 2015 and Nov 1 2016. Eligible children were notified simultaneously but independently by their managing ophthalmologists and paediatricians via the two national active surveillance schemes, the British Ophthalmic and Paediatric Surveillance Units. Standardised detailed data were collected at diagnosis and one year later. Incidence estimates and relative rates by key sociodemographic factors were calculated. Descriptive analyses were undertaken of underlying ophthalmic disorders and nonophthalmic comorbidities. FindingsOf 784 cases, 72% had additional non-ophthalmic impairments/disorders and 4% died within the year. Annual incidence was highest in the first year of life, 5•2 per 10,000 (95% CI 4•7-5•7) with cumulative incidence by 18 years of 10•0 per 10,000 (95% CI 9•4 to 10•8). Rates were higher for those from any ethnic minority group, the lowest quintile of socio-economic status, born preterm or with low birthweight. Only 44% had a single ophthalmic condition: disorders of the brain/visual pathways affected 48% overall. Prenatal or perinatal aetiological factors accounted for 84% of all conditions. InterpretationBCVIS2 provides a contemporary snapshot of the heterogeneity, multi-morbidity and vulnerability associated with childhood visual disability in a high income country, and the arising complex needs. These findings will facilitate developing and delivering healthcare and planning interventional research. They highlight the importance of including childhood visual disability as a sentinel event and metric in global child health initiatives.

Retinal haemorrhages (RH) in a young child suggest child abuse, yet other causes merit consideration. This systematic review addresses non‐traumatic causes of RH in children with one or more overlapping clinical features of abuse (bruising, fractures, intracranial haemorrhage). Searching 12 databases (1950–2009) identified 338 studies for review by two reviewers. Inclusion criteria included: children < 15 years examined by an ophthalmologist detailing retinal findings, confirmed organic cause and exclusion of abuse. Exclusion criteria included: diagnosed coagulopathy, ocular mass lesion and post‐mortem cases. Twenty included studies identified nine relevant conditions (metabolic diseases, bony dysplasias, bleeding disorders and vascular malformations). Where detailed, the RH were bilateral and involved only one area of the retina (the posterior pole). Among proposed confounders of RH, no child with a cough (100 children) or acute life‐threatening event (184 cases) had RH. Just two of 217 children with seizures had posterior pole RH, one unilateral and one bilateral. One cardiopulmonary resuscitation (CPR) study (43 cases) was included where a child with co‐existent clotting abnormalities had tiny (bilateral dot) RH after 60 minutes’ resuscitation. Child abuse remains the commonest cause of RH in young children, although rarer disorders merit consideration. There are insufficient data to conclude that CPR is a confounder in children with RH. Copyright © 2012 John Wiley & Sons, Ltd. Key Practitioner Message Retinal Haemorrhages are strongly associated with Abusive Head Trauma, but have been described in certain medical conditions. Neither cough nor ALTE are associated with RH, which have been found in < 3% of children with seizures. There are inadequate data to conclude that CPR is associated with RH. Case series have reported RH in children who also have clinical features that may overlap with physical abuse, namely certain metabolic, vascular, haematologic disorders and bony dysplasias (specifically osteogenesis imperfecta).

Aim/Background: Abnormal metabolism of the neurotransmitter glutamate is implicated in a number of neurodegenerative conditions. Patients with migraine have been shown to have elevated plasma glutamate levels. Migraine is a risk factor both in terms of prevalence and progression in normal-tension glaucoma (NTG). The aim of this study was to determine whether or not plasma glutamate levels are also elevated in NTG. Methods: Patients were recruited into 2 groups, NTG and control, according to inclusion and exclusion criteria. Patients with migraine were excluded from both groups. Fasting blood samples were collected in lithium heparin tubes, transported on ice, and centrifuged for storage at –21°C. Plasma glutamate levels were measured by an amino acid analyser. Data for each group were compared by applying the Mann-Whitney test. Ethical approval and independent statistical advice for the study was obtained. Results: A total of 27 subjects were recruited: 14 to the NTG group and 13 to the control group. No significant difference was found between the plasma glutamate levels in the 2 groups (p = 0.67). Conclusion: Although an association between normal tension and migraine is recognized, unlike studies in migraine sufferers, this study finds no evidence that patients with NTG have elevated plasma glutamate.