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Selective damage to large cells in the cat retinogeniculate pathway by 2,5-hexanedione

The neurotoxic hexacarbon 2,5-hexanedione (2,5-HD), which produces transport abnormalities and swellings in the large diameter fibers of the peripheral nervous system, was administered to cats in an attempt to produce similar selective effects in the optic tract. Anatomical findings indicate damage to one type of retinal ganglion cell, the large (alpha) or Y-cell class, both during dosing and after a long recovery period. This selective involvement of the large ganglion cells during dosing was shown by decreased retrograde transport of HRP in these cells relative to smaller cells. Such selectivity was not apparent in axonal swellings and neurofilament accumulations which were present in fibers of all diameters in the distal optic tract. Visual threshold studies during dosing showed a loss of flicker resolution with preservation of visual acuity, a result consistent with the different physiological properties of alpha and beta ganglion cells. In one cat, which survived dosing for a period of 8 months, there was a dramatic reduction in the number of large cells and a pronounced shrinkage of those that remained, but no observed changes in other cell types. Thus, this intoxication caused (1) axonal swellings which were not selective for fiber size; (2) a selective defect in axonal transport with later neuronal degeneration and shrinkage that were limited to large cells; and (3) a loss of flicker resolution that may reflect dysfunction of large ganglion cells.