Chronic ischemia induces regional axonal damage in experimental primate optic neuropathy.
OBJECTIVE
To evaluate the effects of chronic optic nerve ischemia in a nonhuman primate model and to evaluate the regional variability of axonal loss.


METHODS
Unilateral ischemic optic neuropathy was induced by administration of endothelin-1 to the retrobulbar space via osmotic pumps in 12 primates for 6 to 12 months. The transversely cut sections were stained and divided into 16 regions. Average axonal density in each region was quantified and compared with the untreated contralateral control eyes.


RESULTS
Mean axonal density was 208 310/mm(2) and 220 661/mm(2) in treated and control eyes, respectively (P = .03, 1-tailed paired t test), for the entire group. Two-way analysis of variance showed a significant effect of endothelin-1 on overall axonal density for the experimental group (P<.001). Among the nerves with significant axonal loss, the mean axonal loss was 11.6% (4%-21%). Regional mapping of the damage showed the axonal loss varied in the damaged nerves; the damaged regions often clustered within specific quadrants.


CONCLUSIONS
Chronic ischemia induced by local administration of endothelin-1 causes significant loss of optic nerve axons with varying regional susceptibility. Clinical Relevance Localized damage occurs in other types of optic neuropathy, such as glaucoma, and may result from regional differences in anatomy, metabolism, or vasculature of the primate optic nerve.
Cioffi
George A
GA
Discoveries in Sight, Devers Eye Institute, Portland, OR 97210, USA. gacioffi@discoveriesinsight.org
Wang
Lin
L
Fortune
Brad
B
Cull
Grant
G
Dong
Jin
J
Bui
Bang
B
Van Buskirk
E Michael
EM
D000818:Animals; D001369:Axons / Q000473:pathology*; D002452:Cell Count; D002908:Chronic Disease; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D007429:Intraocular Pressure; D008253:Macaca mulatta; D009900:Optic Nerve / Q000473:pathology*; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000473:pathology*
D019332:Endothelin-1