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Z. Shao, P. Sapieha, S. Chemtob; The Contribution of Choroidal Involution to Retinal Function Loss in Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3127.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP) represents a major cause of blindness in pediatric populations. Although the disease is thought to stem from an initial dropout in retinal vasculature, little attention has been paid to the contribution of the choroid in the disease process. Remarkably,functional ERG studies reveal geographical discrepancies between areas of vessel loss and those of functional compromise. Here we investigated if choroidal impairment accounted for these inconsistencies.
The rat model of oxygen induced retinopathy (OIR), (80% O2 postnatal day (P) 1-P14) was used to mimic ROP. After hyperoxic exposure, eyes were fixed with paraformaldehyde and cut into sagittal sections for immunohistochemistry (IHC). Lectin staining detected the vasculature and anti-nitrotyrosine antibodies labeled nitration modified proteins in the choroid. Vascular density and morphology was assayed in eye corrosion casts and examined by scanning electron microscopy (SEM). Vessel integrity and leakage was assessed by administering intra-cardiac injections of Evans blue. The contribution of nitric oxide (NO) as a prospective mechanism mediating this degeneration was investigated by administering NO synthase (NOS) inhibitors to the vitreous throughout the hyperoxic period.
Analysis of vascular layers of the eye by IHC revealed a pronounced decrease in central choroidal thickness, which contrasts significantly with the subtle changes observed in the periphery. Consistent with this decay, robust positive staining for nitrotyrosine was observed predominantly in the central choroid of eyes (P12) exposed to hyperoxia for 6 hours. SEM analysis of corrosion casts revealed significant decreases in vessel density in central choroid after hypoxic exposure. Significant increase of albumin bound Evans blue which represents higher plasma leakage, was observed in hyperoxic choroids. Importantly, intravitreal injection of the general NOS inhibitor (N-Nitro-L-Arginine Methyl Ester; L-NAME) and the preferential endothelial NOS (eNOS) inhibitor (L-N-iminoethyl ornithine; L-NIO) were both effective at preserving choroidal vasculature.
The contribution of choroidal vascular decay to the progression of ROP has previously never been disclosed. We demonstrate that hyperoxic exposure of subjects not only interferes with retinal vascular development but also results in a detrimental NOS dependant choroidal degeneration. These findings suggest that effective therapeutic strategies to counter ROP should include choroidal preservation.
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