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D. V. Pow, C. M. Diaz; Neonatal Haemorrhage Evokes Delayed AMD-Like Degeneration in a Rodent Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5416.
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Bleeds in the neonatal human retina are a common event. This study examined the long-term sequelae of such bleeds in pigmented rats that were found to exhibit spontaneous retinal haemorrhages.
Dark Agouti rats (n=96) aged from day of birth to 2 years old were killed with an overdose of sodium pentobarbital (100 mg/kg I.P.). Retinas were fixed with paraformaldehyde and analysed by immunocytochemistry, brightfield and fluorescence microscopy using glial markers such as GFAP and OX42.
Neonatal animals exhibited spontaneous small focal haemorrhages at the vitread surface of the retina. Debris was subsequently cleared by populations of identified macrophages, which then remained in focal patches in the inner retina for the duration of the study. For at least six months after the initial transient bleeds, retinas exhibited no overt histological damage. At around 8-9 months, degenerative changes were apparent in spatial register with the location of the original bleeds. Degenerative changes included formation of photoreceptor rosettes, focal loss of photoreceptors, breakdown of Bruch's membrane, loss of RPE cells, glial remodelling, neovascularisation, ingress of RPE cells (as illustrated by the arrow in the figure) into the retina and accumulation of drusen-like auto-fluorescent structures.
The precise topographic correspondence between sites of initial neonatal bleeds and the subsequent degenerative changes in the adult retina suggest that the two phenomena are linked. Small retinal bleeds around the time of birth may evoke long-lasting consequences that are only manifest in the aged retina. The anatomical features of the lesions are similar to features of AMD. The data reconcile well with the idea that complement Factor H polymorphisms are a risk factor in AMD, since Factor H influences tissue inflammatory responses after haemorrhage. We suggest that these animals may represent a physiologically relevant model for studying AMD.
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