Abstract
BackgroundNiemann-Pick type C1 (NPC1) disease is an inherited lysosomal storage disease caused by mutation of the Npc1 gene, resulting in a progressive accumulation of unesterified cholesterol and glycolipids in lysosomes of multiple tissues and leading to neurodegeneration and other disease. In Npc1 mutant mice, retinal degeneration including impaired visual function, lipofuscin accumulation in the pigment epithelium and ganglion cells as well as photoreceptor defects has been found. However, the pathologies of other individual cell types of the retina in Npc1 mutant mice are still not fully clear. We hypothesized that horizontal cells, amacrine cells, bipolar cells and glial cells are also affected in the retina of Npc1 mutant mice.ResultsImmunohistochemistry and electron microscopy were used to investigate pathologies of ganglion cells, horizontal cells, amacrine cells, bipolar cells, and optic nerves as well as altered activity of glial cells in Npc1 mutant mice.Electron microscopy reveals that electron-dense inclusions are generally accumulated in ganglion cells, bipolar cells, Müller cells, and in the optic nerve. Furthermore, abnormal arborisation and ectopic processes of horizontal and amacrine cells as well as defective bipolar cells are observed by immunohistochemistry for specific cellular markers. Furthermore, hyperactivity of glial cells, including astrocytes, microglial cells, and Müller cells, is also revealed.ConclusionsOur data extend previous findings to show multiple defects in the retina of Npc1 mutant mice, suggesting an important role of Npc1 protein in the normal function of the retina.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-014-0126-2) contains supplementary material, which is available to authorized users.
Highlights
Niemann-Pick type C1 (NPC1) disease is an inherited lysosomal storage disease caused by mutation of the Npc1 gene, resulting in a progressive accumulation of unesterified cholesterol and glycolipids in lysosomes of multiple tissues and leading to neurodegeneration and other disease
Genotype analysis For identification of mice genotype, genomic DNA extracted from about 1 mm long tail of mice with phenol-chloroform was used as a template for polymerase chain reaction (PCR) according to the protocol described previously [2] using the primers suggested by the Jackson Laboratory
Endogenous Npc1 protein in the Npc1+/+ mouse was expressed strongly in the outer plexiform layer (OPL), which consists of the synapses
Summary
Niemann-Pick type C1 (NPC1) disease is an inherited lysosomal storage disease caused by mutation of the Npc gene, resulting in a progressive accumulation of unesterified cholesterol and glycolipids in lysosomes of multiple tissues and leading to neurodegeneration and other disease. The pathologies of other individual cell types of the retina in Npc mutant mice are still not fully clear. Niemann-Pick type C1 disease (NPC1) is a lysosomal storage disorder induced by mutation of Npc gene and characterized by neuronal degeneration [1,2,3]. The mutation of Npc protein causes a progressive accumulation of unesterified cholesterol, phospholipids, glycolipids, and sphingomyelin in lysosomes of multiple tissues, leading to hepatosplenomegaly, tremor, ataxia, dystonia and neurodegeneration. Gliosis and microgliosis have been shown to be especially dominant in the olfactory bulb, which contributes to olfactory deficits [13]
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