Dannhausen, Katharina and Karlstetter, Marcus and Caramoy, Albert and Volz, Cornelia and Jaegle, Herbert and Liebisch, Gerhard and Utermoehlen, Olaf and Langmann, Thomas (2015) Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 464 (2). pp. 434-440. ISSN 0006-291X, 1090-2104
Full text not available from this repository. (Request a copy)Abstract
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(-/-) mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase(-/-) 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(-/-) 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. (C) 2015 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NIEMANN-PICK-DISEASE; SPHINGOLIPID METABOLISM; MASS-SPECTROMETRY; ACTIVATION; LIGHT; MICE; DEGENERATION; PATHOLOGY; Niemann-Pick disease; Acid sphingomyelinase; Microglia; Retina; Inflammation; Lipid accumulation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jun 2019 09:39 |
| Last Modified: | 14 Jun 2019 09:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5002 |
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