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M. Hovakimyan, O. Stachs, M. Reichard, A. Rolfs, J. Lukas, M. Frech, R. F. Guthoff, M. Witt, A. Wree; Ocular Involvement in Niemann-Pick Disease Type C. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5777.
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Niemann-Pick disease type C1 (NPC1) is a fatal neurovisceral lipid storage disease of autosomal inheritance resulting from mutations in the NPC1 gene. In the present study we investigated the involvement of the cornea and retina in NPC1 pathogenesis.
Eleven NPC1 inbred homozygous knock-out mice (NPC1-/-) and 10 age-matched controls (NPC1+/+) were involved. The corneae were investigated by means of in vivo confocal laser-scanning microscopy (CLSM). After enucleation the eyes were processed for histology (Hematoxylin/eosin and filipin staining) and electron microscopy, and corneae and retinae were examined.
Changes of the corneal epithelial cells in form of hyperreflective intracellular deposits were detected in NPC1-/- mice using in vivo CLSM. These changes were limited only to the corneal epithelium, whereas the other corneal structures did not differ between NPC1+/+ and NPC1-/- mice.H.E. staining revealed no differences in the morphology of corneae and retinae between NPC1+/+ and NPC1-/- mice. Filipin stainig showed cholesterol accumulation in different layers of the retina but not in the cornea of NPC1-/- mice. The most pronounced cholesterol accumulation was detected in the ganglion cell layer. The ultrastructural analysis revealed 200-500 nm vacuolated cytoplasmic structures loaded with electron - dense material in the corneal epithelium and keratocytes. Many of these inclusions bodies appeared as enlarged cisterns of endoplasmic reticulum. The same structures were detected in the inner nuclear and plexiform and ganglionic cell layers of the retina. In accordance with filipin staining, the most pronounced accumulation was revealed in the ganglion cell layer.
For the first time, the corneal involvement in NPC1 disease was shown in knock-out mice using a non-invasive in vivo CLSM. The ultrastructural analysis showed that not only the cornea but also the retina is changed in NPC1 disease. Specific detection of cholesterol accumulation was shown only in the retina.
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