title: Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB.
abstract: 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 46 th 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.
authors.affiliation: Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston  TX, USA.|School of Optometry, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: Dennis Y
authors.initials: DY
authors.lastname: Tse
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Jan and Dun Duncan Neurological Research Institute, Texas Children's Hospital, Houston TX, USA.
authors.forename: Parisa
authors.initials: P
authors.lastname: Lotfi
authors.affiliation: Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston  TX, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Simons
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Jan and Dun Duncan Neurological Research Institute, Texas Children's Hospital, Houston TX, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Sardiello
authors.affiliation: Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston  TX, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Wu
mesh_terms: D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D004596:Electroretinography; D007150:Immunohistochemistry; D051379:Mice; D017628:Microglia / Q000473:pathology*; D009084:Mucopolysaccharidosis III / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D010775:Photic Stimulation; D012162:Retinal Degeneration / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D012174:Retinitis Pigmentosa / Q000473:pathology* / Q000503:physiopathology*