Involvement of Retinal Neurons and Pigment Epithelial Cells in a Murine Model of Sandhoff Disease

Background/Aims: 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 withconcanavalin 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. Conclusion: 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.