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S. F. Oster, D. S. McLeod, T. Otsuji, M. F. Goldberg, G. A. Lutty; Retinal Vascular Abnormalities in NEMO-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3998.
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Incontinentia pigmenti (IP) is a male-lethal X-linked dominant genodermatosis that in affected females can lead to retinal vaso-occlusion, ischemia, and ultimately neovascular retinopathy. Soon after human genetic studies showed that mutations in the NEMO gene account for most cases of human IP, mice with targeted NEMO mutations were developed. These animals share the characteristic skin lesions of human IP (Makris et al, Molecular Cell 2000), but their retinal phenotype has not been characterized. This study examines the retinal vasculature of NEMO mutant mice, and aims to understand the vaso-occlusive mechanisms at work in IP.
A series of 18 heterozygous NEMO-deficient female C57/Bl6 mice with ages ranging from post-natal day 8 thru 6.5 months of life were studied. Eyes were processed and sectioned either whole or as retinal flat mounts, and stained with Hematoxylin & Eosin and Periodic Acid Schiff to study retinal vascular detail. Additionally, a sub-set of retinas were incubated with ADPase to evaluate histochemical changes, the vascular pattern, and endothelial viability.
Several experimental eyes exhibited persistent fetal vasculature, including remnants of anterior and posterior hyaloid structures. More strikingly, as mice matured past 1 month of age, retinal arteriolar abnormalities became evident. Global assessment of the retinal vasculature with ADPase staining showed increased tortuosity, and microscopic examination revealed arteriolar luminal narrowing due to redundancy of the vascular endothelial cells and thickening of their basement membrane. Venous morphology was normal.
This study characterizes the retinal phenotype of heterozygous NEMO deficient female mice. There is evidence of persistent fetal vasculature, consistent with findings in human IP, and of retinal arteriolar abnormalities, including luminal narrowing, endothelial cell changes, basement membrane thickening, and vascular tortuosity.
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