Abstract:
Preferential loss of large axons has been cited as a characteristic of glaucomatous optic neuropathy (GON). The purpose of this study is to determine if there is differential loss of large vs. small axons in three different experimental glaucoma models in Macaque monkeys.
Three types of experimental GON were induced 1) chronic optic nerve ischemia via the vasoconstrictor, endothelin–1 to the optic nerve (ET–1, n=6) , 2) elevated IOP by trabecular meshwork lasering (High IOP, n=3), and 3) a combination of the two (ET–1 + High IOP, n=5). For each of the models, one eye was treated and the contralateral eye served as control. Cross–sections of all the optic nerves from the monkeys were processed and stained for axons with phenylendiamine. Axons were counted and the area of each axon was measured using an semi– automated image analysis system (Bioquant Imaging Systems, Nashville, TN). For each animal the axons in the control eye were separated into small and large axons and cumulative frequency distributions were plotted. The axon sizes were used to bin the frequency of all axons in the treatment eye. The ratio of frequency of the small and large axon groups of the treated eye over the control eye was calculated to determine if there was differential loss of small or large axons in each of the models.
In the control eyes of the models, 80% of the axons were smaller than 0.97+/– 0.26 µm2 (ET–1), 0.68 +/– 0.03 µm2 (High IOP) and 0.67 +/– 0.09 µm2 (ET + High IOP), respectively. In the ET–1 treated eyes, there was fewer large axons than the control eyes (p=0.02). In the High IOP model there were fewer small (p=0.04) and large (p=0.05) axons. In the combined ET–1+ High IOP treated eyes there was fewer small axons (p=0.007).
The size of axons, which are damaged in the three models, varies between the models. While the data is based on a small number of animals, significant differential loss is seen in each model. It is interesting that the combination of ischemia and High IOP has a differential loss of axons that is not similar to either the ET–1 or High IOP model alone.
Keywords: optic disc • ischemia • intraocular pressure