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Title: Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice.more » • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.« less
Authors:
; ;  [1] ; ;  [2] ;  [3] ;  [4] ;  [1]
  1. Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany)
  2. Department of Ophthalmology, University Hospital Regensburg, Regensburg (Germany)
  3. Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg (Germany)
  4. Institute for Medical Microbiology, Immunology and Hygiene and Center for Molecular Medicine Cologne, University of Cologne, Cologne (Germany)
Publication Date:
OSTI Identifier:
22462198
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 464; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOMEDICAL RADIOGRAPHY; BRAIN; DEPOSITS; DISEASES; GENES; IN VIVO; INFLAMMATION; MICE; MUTATIONS; PATIENTS; PHAGOCYTES; PHOSPHOLIPIDS; RETINA; STAINS