title: Defects in the retina of Niemann-pick type C 1 mutant mice.
abstract: 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.
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Strasse 20, D-18147, Rostock, Germany. xin.yan@med.uni-rostock.de.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Strasse 20, D-18147, Rostock, Germany. lucy.ma.28@gmail.com.
authors.forename: Lucy
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, F.-Barnewitz Strasse 4, D-18119, Rostock, Germany. marinahovakimyan@yahoo.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Hovakimyan
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Strasse 20, D-18147, Rostock, Germany. jan.lukas@med.uni-rostock.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Lukas
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstrsse 9, D-18055, Rostock, Germany. anderas.wree@med.uni-rostock.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.affiliation: Electron Microscopy Center, Rostock University Medical Center, Strempelstr. 14, D-18057, Rostock, Germany. marcus.frank@med.uni-rostock.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Frank
authors.affiliation: Department of Ophthalmology, Rostock University Medical Center, Doberaner Strasse 140, D-18057, Rostock, Germany. rudolf.guthoff@med.uni-rostock.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Guthoff
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Strasse 20, D-18147, Rostock, Germany. arndt.rolfs@med.uni-rostock.de.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstrsse 9, D-18055, Rostock, Germany. martin.witt@med.uni-rostock.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Witt
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Rostock University Medical Center, Gehlsheimer Strasse 20, D-18147, Rostock, Germany. jiankai.luo@uni-rostock.de.
authors.forename: Jiankai
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism / Q000473:pathology*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins