Journal of Neuroscience, Vol 5, 1641-1652, Copyright © 1985 by Society for Neuroscience
Selective damage to large cells in the cat retinogeniculate pathway by 2,5-hexanedione
T Pasternak, DG Flood, TA Eskin and WH Merigan
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.