Histomorphometric analysis of optic nerve changes in experimental glaucoma

Purpose: To assess relative changes in different tissue components of optic nerve and their relationship to nerve fiber loss in the experimental monke y model of glaucoma. Methods: Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the right eye of eight monkeys (Macaca fascicularis). Bo th experimental right optic nerves and control left optic nerves were studi ed. Histomorphometrics analysis was performed on optic nerve cross-sections using bright field microscopy with camera lucida. Cross-sectional areas of optic nerve tissue components were estimated by point counting, Nerve fibe r density was estimated by unbiased random sampling. Nerve fiber number was calculated by multiplying nerve fiber density with neuroglial area. Results: Varying degrees of nerve fiber loss were seen in eight optic nerve s with chronic IOP elevation. More than 50% nerve fiber loss was noted in f our of eight experimental optic nerves. In these severely affected optic ne rves, total optic nerve area was significantly decreased compared with cont rol optic nerves. Among the optic nerve tissue components, only the ratio o f myelinated fiber area to total optic nerve area was significantly decreas ed. The ratio of extraaxonal area to total optic nerve area was significant ly increased, whereas the ratio of interfascicular septal area to total opt ic nerve area did not change significantly. For all optic nerves, differenc es in nerve fiber count between control and experimental optic nerves showe d the strongest correlation with differences in myelinated fiber area, foll owed by differences in extraaxonal area and total optic nerve area. Conclusion: This histomorphometric study suggests the validity of the exper imental monkey model of glaucoma in studying changes occurring in the nonax onal optic nerve tissue components in human glaucomatous optic neuropathy. Glial scar tissue area was significantly increased in optic nerves with sev ere glaucomatous damage. Although a decrease in total optic nerve area was observed, among the optic nerve tissue components only myelinated nerve fib er area decreased significantly. Myelinated nerve fiber area also showed th e strongest association with nerve fiber loss in experimental glaucoma.