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Hana Levkovitch–Verbin, Harry A. Quigley, Lisa A. Kerrigan–Baumrind, Sam A. D’Anna, Danielle Kerrigan, Mary Ellen Pease; Optic Nerve Transection in Monkeys May Result in Secondary Degeneration of Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2001;42(5):975-982.
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purpose. Interest in neuroprotection for optic neuropathies is, in part, based
on the assumption that retinal ganglion cells (RGCs) die, not only as a
result of direct (primary) injury, but also indirectly as a result of
negative effects from neighboring dying RGCs (secondary degeneration).
This experiment was designed to test whether secondary RGC degeneration
occurs after orbital optic nerve injury in monkeys.
methods. The superior one third of the orbital optic nerve on one side was
transected in eight cynomolgus monkeys (Macaca
fascicularis). Twelve weeks after the partial transection, the
number of RGC bodies in the superior and inferior halves of the retina
of the experimental and control eyes and the number and diameter of
axons in the optic nerve were compared by detailed histomorphometry.
Vitreous was obtained for amino acid analysis. A sham operation was
performed in three additional monkeys.
results. Transection caused loss of 55% ± 13% of RGC bodies in the superior
retina of experimental compared with fellow control eyes (mean ±
SD, t-test, P < 0.00,001, n= 7). Inferior RGCs, not directly injured by transection,
decreased by 22% ± 10% (P = 0.002). The loss of
superior optic nerve axons was 83% ± 12% (mean ± SD, t-test, P = 0.0008, n= 5) whereas, the inferior loss was 34% ± 20%
(P = 0.02, n = 5). Intravitreal
levels of glutamate and other amino acids in eyes with transected
nerves were not different from levels in control eyes 12 weeks after
injury. Fundus examination, fluorescein angiography, and histologic
evaluation confirmed that there was no vascular compromise to retinal
tissues by the transection procedure.
conclusions. This experiment suggests that primary RGC death due to optic nerve
injury is associated with secondary death of surrounding RGCs that are
not directly injured.
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