Ultrastructure of the retina in Tay-Sach's disease.

TAY-SACHS'S disease is an hereditary disorder of lipid metabolism characterized by a biochemical abnormality which leads to the deposition of large amounts of a monosialoganglioside (acyl-sphingosine-N-triose-N-acetylneuraminic acid), which normally constitutes only a very small fraction of the total cerebral gangliosides, in ganglion cells of the central nervous system. The exact nature of the inborn error of metabolism which gives rise to this abnormal storage of lipid is unknown, but it is probably a defect in the normal catabolic pathway of the ganglioside which leads to its accumulation (Svennerholm, 1962). Ganglioside deposition causes ballooning and death of the ganglion cells, which is accompanied by Wallerian degeneration of their axons and widespread massive glial proliferation (Fredrickson and Trams, 1966). The neuro-retina, embryologically a part of the central nervous system, shares in these destructive changes, and the deposition of ganglioside in the retinal ganglion cells, where they are most numerous in the parafoveal area, gives rise to the characteristic cherry-red spot appearance on ophthalmoscopy. The light-microscopical appearances of the cerebral and retinal tissues in this disorder have long been well recognized, but the ultrastructure of cerebral biopsy specimens from cases of Tay-Sachs's disease has only recently been described (Terry and Weiss, 1963). The characteristic feature is the presence of round or oval membranous cytoplasmic bodies (MCB), principally in the cytoplasm of the cerebral ganglion cells but also in glial cells and perivascular tissue cells. These bodies appear to be unconnected with the ribosomes, mitochrondria, and reticulum of the affected cell, which are normal in structure. The membranous cytoplasmic bodies, varying from 0'5 to 2-0 p in diameter, have a unique appearance, consisting of concentric layers of electron dense material. They have been harvested by centrifugation techniques from homogenates of the brain tissue of patients who have died with Tay-Sachs's disease (Samuels, Korey, Gonatas, Terry, and Weiss, 1963) and have been found to consist mainly of gangliosides, cholesterol, and phosphatides. The gangliosides which they contain have solubility characteristics very similar to those isolated from Tay-Sachs's brain tissue (Terry and Korey, 1960). It seems likely that these structures are formed by a spontaneous aggregation of molecules of lipid, particularly of gangliosides, which have accumulated because of the metabolic defect and have become orientated to form membranes. When the ganglion cells die because of interference with their normal metabolic processes, the membranous cytoplasmic bodies are phagocytosed