Optic nerve transection in monkeys may result in secondary degeneration ofretinal ganglion cells

PURPOSE. Interest in neuroprotection for optic neuropathies is, in part, ba sed 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 nega tive effects from neighboring dying RGCs (secondary degeneration). This exp eriment was designed to test whether secondary RGC degeneration occurs afte r 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 a fter 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 h istomorphometry. Vitreous was obtained for amino acid analysis. h sham oper ation was performed in three additional monkeys. RESULTS. Transection caused loss of 55% +/- 13% of RGC bodies in the superi or retina of experimental compared with fellow control eyes (mean +/- SD, t -test, P < 0.00,001, n = n. Inferior RGCs, not directly injured by transect ion, decreased by 22% <plus/minus> 10% (P = 0.002). The loss of superior op tic nerve axons was 83% +/- 12% (mean +/- SD, t-test, P = 0.0008, n = 5) wh ereas, the inferior loss was 34% +/- 20% (P = 0.02, n = 5). Intravitreal le vels of glutamate and other amino acids in eyes with transected nerves were not different from levels in control eyes 12 weeks after injury. Fundus ex amination, fluorescein angiography, and histologic evaluation confirmed tha t there was no vascular compromise to retinal tissues by the transection pr ocedure. CONCLUSIONS. This experiment suggests that primary RGC death due to optic n erve injury is associated with secondary death of surrounding RGCs that are not directly injured.