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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. [ABSTRACT FROM AUTHOR]

The introduction of disease-specific therapy for patients with type I Gaucher disease (GD1) was a revolution in the management of patients, but not without cost. Thus, the management of mildly affected patients is still debated. We herein report a long-term follow-up (median (range) of 20 (5–58) years) of 103 GD1 patients who have never received enzymatic or substrate reduction therapy. The median (range) platelet count and hemoglobin levels in last assessment of all but six patients who refused therapy (although recommended and approved) were 152 (56–408) × 103/mL and 13.1 (7.6–16.8) g/dL, respectively. Most patients had mild hepatosplenomegaly. Nine patients were splenectomized. No patient developed clinical bone disease. The median (range) lyso-Gb1 levels at last visit was 108.5 (8.1–711) ng/mL; lowest for patients with R496H/other and highest for patients refusing therapy. This rather large cohort with long follow-up confirms that mildly affected patients may remain stable for many years without GD-specific therapy. The challenge for the future, when newborn screening may detect all patients, is to be able to predict which of the early diagnosed patients is at risk for disease-related complications and therefore for early treatment, and who may remain asymptomatic or minimally affected with no need for disease-specific therapy. [ABSTRACT FROM AUTHOR]