Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB

Sanfilippo syndrome Type B or Mucopolysaccharidosis IIIB (MPS IIIB) is a neurodegenerative autosomal recessive lysosomal storage disorder in which patients suffer severe vision loss from associated retinopathy. Here we sought to study the underlying retinal functional and morphological changes assoc...

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Bibliographic Details
Published in:Scientific reports 2015-11, Vol.5 (1), p.17143-17143, Article 17143
Main Authors: Tse, Dennis Y., Lotfi, Parisa, Simons, David L., Sardiello, Marco, Wu, Samuel M.
Format: Article
Language:English
Subjects:
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Animals
Cell Count
Disease Models, Animal
Electrophysiological Phenomena
Electroretinography
Humanities and Social Sciences
Immunohistochemistry
Mice
Microglia - pathology
Mucopolysaccharidosis III - complications
Mucopolysaccharidosis III - pathology
Mucopolysaccharidosis III - physiopathology
multidisciplinary
Photic Stimulation
Retinal Degeneration - complications
Retinal Degeneration - pathology
Retinal Degeneration - physiopathology
Retinitis Pigmentosa - pathology
Retinitis Pigmentosa - physiopathology
Science
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Summary:Sanfilippo syndrome Type B or Mucopolysaccharidosis IIIB (MPS IIIB) is a neurodegenerative autosomal recessive lysosomal storage disorder in which patients suffer severe vision loss from associated retinopathy. Here we sought to study the underlying retinal functional and morphological changes associated with MPS IIIB disease progression using the established model of MPS IIIB, the B6.129S6-Naglu(tm1Efn)/J mouse line. Electroretinogram (ERG) was recorded from MPS IIIB and wild-type (WT) mice at the age of 28 and 46 weeks and retinal tissues were subsequently collected for immunohistochemistry analysis. At the 28th week, rod a- and b-wave amplitudes were significantly diminished in MPS IIIB compared to WT mice. The cone a- and b-waves of MPS IIIB mice were not significantly different from those of the control at the 28th week but were significantly diminished at the 46th week, when MPS IIIB mice showed a major loss of rods and rod bipolar cells in both central and peripheral regions and a minor loss of cones in the periphery. Activation of microglia and neovascularization were also detected in the MPS IIIB retina. The new findings that cones and rod bipolar cells also undergo degeneration and that retinal microglia are activated, will inform future development of therapeutic strategies.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep17143