Long-term retinal PEDF overexpression prevents neovascularization in a murine adult model of retinopathy

Neovascularization associated with diabetic retinopathy (DR) and other ocular disorders is a leading cause of visual impairment and adult-onset blindness. Currently available treatments are merely palliative and offer temporary solutions. Here, we tested the efficacy of antiangiogenic gene transfer in an animal model that mimics the chronic progression of human DR. Adeno-associated viral (AAV) vectors of serotype 2 coding for antiangiogenic Pigment Epithelium Derived Factor (PEDF) were injected in the vitreous of a 1.5 month-old transgenic model of retinopathy that develops progressive neovascularization. A single intravitreal injection led to long-term production of PEDF and to a striking inhibition of intravitreal neovascularization, normalization of retinal capillary density, and prevention of retinal detachment. This was parallel to a reduction in the intraocular levels of Vascular Endothelial Growth Factor (VEGF). Normalization of VEGF was consistent with a downregulation of downstream effectors of angiogenesis, such as the activity of Matrix Metalloproteinases (MMP) 2 and 9 and the content of Connective Tissue Growth Factor (CTGF). These results demonstrate long-term efficacy of AAV-mediated PEDF overexpression in counteracting retinal neovascularization in a relevant animal model, and provides evidence towards the use of this strategy to treat angiogenesis in DR and other chronic proliferative retinal disorders

Adherence to management guidelines for growth faltering and anaemia in remote dwelling Australian Aboriginal infants and barriers to health service delivery

Background: Remote dwelling Aboriginal infants from northern Australia have a high burden of disease and frequently use health services. Little is known about the quality of infant care provided by remote health services. This study describes the adherence to infant guidelines for anaemia and growth faltering by remote health staff and barriers to effective service delivery in remote settings. Methods: A mixed method study drew data from 24 semi-structured interviews with clinicians working in two remote communities in northern Australia and a retrospective cohort study of Aboriginal infants from these communities, born 2004-2006 (n = 398). Medical records from remote health centres were audited. The main outcome measures were the period prevalence of infants with anaemia and growth faltering and management of these conditions according to local guidelines. Qualitative data assessed clinicians' perspectives on barriers to effective remote health service delivery. Results: Data from 398 health centre records were analysed. Sixty eight percent of infants were anaemic between six and twelve months of age and 42% had documented growth faltering by one year. Analysis of the growth data by the authors however found 86% of infants experienced growth faltering over 12 months. Clinical management and treatment completion was poor for both conditions. High staff turnover, fragmented models of care and staff poorly prepared for their role were barriers perceived by clinicians' to impact upon the quality of service delivery. Conclusion: Among Aboriginal infants in northern Australia, malnutrition and anaemia are common and occur early. Diagnosis of growth faltering and clinicians' adherence to management guidelines for both conditions was poor. Antiquated service delivery models, organisation of staff and rapid staff turnover contributed to poor quality of care. Service redesign, education and staff stability must be a priority to redress serious deficits in quality of care provided for these infants