Ischemic model of optic nerve injury.
OBJECTIVE
It is proposed that the anterior optic nerve is specifically susceptible to microcirculatory compromise contributing to the development of glaucomatous optic neuropathy.


METHODS
Ischemic optic neuropathy was induced by delivering endothelin-1 (ET-1) to the retrobulbar space in one eye of 12 primates for 6 to 12 months. Regional ganglion cell axonal sizes and densities were compared with the normal, contralateral eyes.


RESULTS
Without changes of intraocular pressure, mean axonal density was significantly decreased in ET-1 eyes compared to controls (P = .03, paired t test). Two-way matched-pair analysis of variance showed a significant effect of ET-1 on overall axonal density (P < .0001). Among the animals with significant axonal loss, the mean axonal loss was 11.6%, and loss varied from 4% to 21%. Axonal loss was commonly localized within specific quadrants. Five animals were examined for preferential axonal size loss. As a group, there appears to be a tendency toward preferential large axonal loss, but the mean axonal loss of large and small axons did not meet significant differences (P = .1) However, examination of individual animals with significant loss shows significantly greater loss of large axons as compared to the small axons in three of the animals.


CONCLUSIONS
Chronic optic nerve ischemia causes demonstrable and localized damage of the optic nerve, without intraocular pressure elevation. There is preferential loss of large retinal ganglion cell axons in animals with significant axonal loss. Ischemia-induced focal axonal loss is similar to human glaucoma and may represent a differential regional vulnerability.
Cioffi
George A
GA
Devers Eye Institute, Portland, Oregon, USA.
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000008:administration & dosage; D005123:Eye; D005260:Female; D005901:Glaucoma / Q000473:pathology; D007260:Infusion Pumps; D007429:Intraocular Pressure; D008253:Macaca mulatta; D009900:Optic Nerve / Q000648:ultrastructure; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000648:ultrastructure*
D019332:Endothelin-1