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Dennis Yan-Yin Tse, Parisa Lotfi, Marco Sardiello, Samuel Wu; Retinal microglial activation in a mouse model of Sanfilippo Syndrome. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):428.
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© ARVO (1962-2015); The Authors (2016-present)
Sanfilippo syndrome or Mucopolysaccharidosis III (MPS-III) is a neurodegenerative autosomal recessive lysosomal storage disorder in which patients suffer progressive vision loss. Previous studies have reported aberrant lysosome storage in the retinal pigment epithelium and in non-neuronal cells of the inner retina. Degenerations of photoreceptors and rod bipolar cells were also found. We hypothesize that inflammatory response is involved in the process and we sought to characterize it in this study.
B6.129S6-Naglutm1Efn/J, the mouse model of the MPSIIIB, and age-matched wildtype (WT) mice were purchased from the Jackson lab. Mice (4/group) were sacrificed at the 46th week for immunohistochemistry, in which staining was performed using double-labeling procedures on whole-mount retina with antibodies for Iba-1 (activated microglia), GFAP (astrocyte, Muller cells) and Isolectin-B4 (Leukocytes/macrophages). Images of the whole-mounted retina were acquired using the tile-scan feature of the Zeiss Zen software with a motorized platform and a 10x objective under a Zeiss LSM700 confocal microscope. Immunoreactive cell number and cell occupied area were analyzed using ImageJ Software. Scotopic flash eletroretinogram (ERG) and paired flash ERG were recorded from another age-matched cohort.
At 46 week of age, knockout (KO) mice exhibited significantly decreased scotopic ERG a-wave and b-wave, as well as diminished cone a-wave and b-wave.<br /> The number of Iba-1 positive cells was significantly higher in the KO compared to the WT (Mean ±SEM: 350 ±53.0 vs 123 ±18.4). The total area occupied by Iba-1+ cells was also larger in the knockout mice compared to the WT (Mean ±SEM: 1763 ±263.9 vs 972 ±109.3). Iba-1+ cells in KO retina formed a denser cellular mosaic. Secondary and superior order processes were also more pronounced in KO retina. GFAP and Isolectin-B4 immunohistochemistry results are under investigated.
Morphological signs of retina microglial activation were evident in the late stage of Sanfilippo syndrome. The relationships between activated microglial, inflammatory responses and degeneration of retinal neurons are under investigation.
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