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B.J. Winn, D.S. Pereira, J. Wong, R. Bhisitkul; Retinal Toxicity Induced by Subretinal vs. Sub–RPE Hemorrhage in a Rabbit Model of Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):243.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:While recent therapies for exudative age–related macular degeneration (AMD) have targeted choroidal neovascularization (CNV), the complications of CNV such as subretinal hemorrhage (SRH) have received less attention. SRH produces damage to the neurosensory retina via toxic, ischemic, and fibrotic mechanisms.(1,2) Surgical and pharmacologic evacuations of SRH have been employed in the past in an attempt to minimize such damage. In order to assess potential neuroprotective therapies, a rabbit model of SRH and sub–RPE hemorrhage is used to determine the histopathologic characteristics and time course of blood–induced retinal toxicity. Methods:In anesthetized adult New Zealand White rabbits, 100 uL of autologous whole blood was injected via an angled 30–gauge needle introduced transclerally into the vitreous cavity and then into either the subretinal or sub–RPE space near the optic nerve. At 24 hours, 48 hours, 4 days and 7 days after injections, the eyes were enucleated and fixed in 2.5% gluteraldehyde and 1.5% paraformaldehyde in 0.1M sodium cacodylate buffer solution for at least 24 hours. The retinas were then embedded in plastic, sectioned, and stained with hematoxylin and eosin for light microscopy. Results:Autologous subretinal blood was found on histology to produce neuronal toxicity confined to the photoreceptor outer segments and the outer nuclear layer. Photoreceptor outer segments were severely shortened or eliminated, and the outer nuclear layer displayed disorganization and thinning, loss of cells, and decreased number of cells per row. Toxicity was seen at 48 hours after SRH; at 24 hours no retinal damage was detectable. By one week outer nuclear layer damage was essentially complete. Toxicity appeared to be specific; no mechanical effects were observed, nor were subretinal fibrosis and traction seen. In comparison, sub–RPE hemorrhage did not produce significant toxicity at 24 hours, 48 hours, or 7 days. Conclusions:Subretinal hemorrhage produces specific photoreceptor toxicity within 48 hours. Retinal toxicity appears to be mediated by contact with blood, as the retina was relatively unaffected by sub–RPE hemorrhage. The findings suggest that short–term retinal damage is mediated primarily by direct toxic effects rather than ischemia, inflammation, or fibrotic traction. Using this model, neuroprotective therapies against hemorrhage–induced retinal toxicity can be investigated. 1 Zarbin MA. Arch Ophthalmol. 2004 Apr;122(4):598–614. 2 de Juan E Jr, Machemer R. Am J Ophthalmol. 1988 Jan 15;105(1):25–9.
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