Involvement of retinal neurons and pigment epithelial cells in a murine model of sandhoff disease.
OBJECTIVE
To investigate the effects of deficient degradation of glycolipids on the morphological appearance of all retinal cells in a murine model of G(M2) gangliosidosis (Sandhoff disease).


METHODS
The morphological appearance of the retina in Sandhoff mice at symptomatic stages (3 and 4 months of age) was examined by immunohistochemistry, lectin histochemistry and electron microscopy.


RESULTS
Under a light microscope, intense immunoreactivity for G(M2) ganglioside was observed in the ganglion cell, inner plexiform, and inner nuclear layers in the Sandhoff mice. The ganglion cell layers and retinal pigment epithelium in the Sandhoff mice were stained intensely with concanavalin A agglutinin and succinylated wheat germ agglutinin. Ultrastructural studies revealed numerous inclusions in the cytoplasm of retinal ganglion cells and other neuronal cells (particularly amacrine cells), whereas we failed to detect apparent involvement of photoreceptor cells. In addition to the cytoplasmic inclusions in the retinal neurons, vacuolation was evident in the retinal pigment epithelium.


CONCLUSIONS
These findings suggest that neuronal cells and pigment epithelial cells are more vulnerable to the deficient ganglioside degradation than other retinal cells in Sandhoff mice.
Sango
Kazunori
K
Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan. kazsango@tmin.ac.jp
Yamanaka
Shoji
S
Ajiki
Kyoko
K
Arai
Nobutaka
N
Takano
Masahiko
M
D000818:Animals; D004195:Disease Models, Animal; D005678:G(M2) Ganglioside / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051379:Mice; D016253:Microscopy, Immunoelectron; D009475:Neurons, Afferent / Q000378:metabolism / Q000648:ultrastructure*; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000648:ultrastructure*; D012160:Retina / Q000648:ultrastructure*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000648:ultrastructure*; D012497:Sandhoff Disease / Q000473:pathology*
D005678:G(M2) Ganglioside