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Background/aims: Premature infants are born with incompletely vascularised retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of prenatal and postnatal body growth is important in the pathogenesis of ROP. The aim of this study was to develop a physiology-based rat model in order to study the effect of growth restriction and oxygen on early retinal vascular development., Methods: Rat mothers were fed either a normal (18% casein) or low (9% casein) protein diet (to cause pup growth restriction) from the last week of gestation. After birth, mother and pups were placed in either room air or a specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen profile. The oxygen profile was based on that from a premature infant who developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained using biotinylated lectin. Images were captured by confocal microscopy. The avascular areas of the retinas were measured and compared., Results: Growth restricted rat pups had significantly larger retinal avascular areas than 'normally grown' rat pups (Mann-Whitney U test, p<0.001). Growth restricted rat pups raised in fluctuating oxygen had significantly larger retinal avascular areas than growth restricted rat pups raised in room air (Mann-Whitney U test, p=0.001)., Conclusions: The authors have developed a novel model for ROP that involves inducing both intrauterine and postnatal growth restriction and also exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can be used to study the effects of growth, nutrition and oxygen on early retinal vascular development.

Aim: To assess the role of clusterin in retinal vascular development and in free radical damage in vivo and in vitro., Methods: The expression of clusterin, von Willebrand factor (vWF), flk-1, heat shock protein 27 (Hsp27) and heat shock protein 70 (Hsp70) was examined in the retinas of developing mice and oxygen-induced retinopathy (OIR) mice by immunofluorescence staining and western blot analysis. Hydrogen peroxide (H(2)O(2))-pretreated human retinal endothelial cells (HREC) and astrocytes were cultured in the presence or absence of exogenous clusterin, and then the cell viability was measured using the MTT assay and DAPI staining., Results: Clusterin was expressed mainly in the inner retina and co-localised with vWF, an endothelial cell marker. During the mouse developmental process, clusterin expression was decreased, which was similar to the expression of flk-1, vWF and Hsp27. Furthermore, in the OIR model, clusterin expression changed in a similar way to both vWF and Hsp27. Under hypoxic conditions, clusterin expression increased in HREC and astrocytes. In H(2)O(2)-pretreated HREC and astrocytes, clusterin protected against apoptotic cell death., Conclusions: These results suggest that clusterin is associated with protection from apoptotic retinal cell death in retinal development and in free radical damage.

By cannulating the stroma of rabbit corneae, and introducing extracts of retina and vitreous from newborn kittens subjected to vaso-obliterative doses of oxygen, an attempt was made to test the hypothesis that ischaemic retinal tissue releases a factor with vasoformative properties. It was found that, although retino-vitreal extracts from the test animals elicited a positive response in just over half the experiments, the degree of corneal vascularisation provoked by extracts from intact control animals was only marginally less. Consequently our findings do not permit any definite answer regarding the existence of a specific factor responsible for the proliferation of new vessels on the retinal surface in states associated with retinal hypoxia.

Maintenance of newborn kittens in an oxygen rich atmosphere followed by a recovery period in a normal atmosphere mimicked the effects of the human disease retrolental fibroplasia. The retinas of such kittens contained significantly raised levels of low molecular weight angiogenic material (as measured by procollagenase activation) when compared with those of a control group of kittens.