Defects in the retina of Niemann-pick type C 1 mutant mice

BMC Neuroscience

Jiankai Luo¹  Martin Witt³  Arndt Rolfs¹  Rudolf Guthoff⁴  Marcus Frank⁵  Andreas Wree³  Jan Lukas¹  Marina Hovakimyan²  Lucy Ma¹  Xin Yan¹ 

[1] Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Strasse 20, Rostock, D-18147, Germany;Institute for Biomedical Engineering, Rostock University Medical Center, F.-Barnewitz Strasse 4, Rostock, D-18119, Germany;Department of Anatomy, Rostock University Medical Center, Gertrudenstrsse 9, Rostock, D-18055, Germany;Department of Ophthalmology, Rostock University Medical Center, Doberaner Strasse 140, Rostock, D-18057, Germany;Electron Microscopy Center, Rostock University Medical Center, Strempelstr. 14, Rostock, D-18057, Germany

关键词: Neurodegeneration;    Optic nerve;    Retina;    Npc1;   

Others  :  1090465
DOI  :  10.1186/s12868-014-0126-2

 received in 2014-06-19, accepted in 2014-11-12,  发布年份 2014

【 摘 要 】

Background

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. 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.

Results

Immunohistochemistry 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.

Conclusions

Our 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.

【 授权许可】

   
2014 Yan et al.; licensee BioMed Central Ltd.

【 图 表 】

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