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Optic Nerve Transection in Monkeys May Result in Secondary Degeneration of Retinal Ganglion Cells

From the Glaucoma Research Laboratory, Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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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