Abstract
Abstract: :
Purpose:To evaluate the relationship between vitreous glutamate concentration ([glutamate]) and axon loss in experimental glaucoma in monkeys. Methods:Unilateral chronic glaucoma was induced in 18 rhesus and 9 cynomolgus monkeys by argon laser scarification of the trabecular meshwork. Intraocular pressures (IOP) were monitored weekly by applanation tonometry. Optic nerve damage was assessed by stereoscopic slitlamp biomicroscopy and fundus photography. Vitreous sampling was done just prior to enucleation of all eyes. Processing included analysis of the vitreous for [glutamate] by HPLC, and quantification of axon loss after histopathologic sectioning of the optic nerve. The relationship between [glutamate] in glaucomatous vs. fellow control eyes was evaluated by comparing median ratios of [glutamate] (T), and using the paired-sample sign test to test the null hypothesis that T ≤ 1. Spearman rank correlation was used to assess correlation of [glutamate], axon count, IOP, C/D ratio, duration of IOP elevation, and age. Results:The median ratio of [glutamate] in a glaucomatous eye to its control eye was 1.08 (p=0.15 for ratio greater than 1.0). [Glutamate] from peak height on HPLC ranged from 2.97-89.7 µM in study eyes, and 2.57-89.0 µM in control eyes. Axon counts ranged from 350,498-1,168,830 in study eyes, and 754,874-1,715,868 in control eyes. Mean IOP ranges were 19.7-62.1 mmHg in study eyes, and 12.4-25.0 mmHg in control eyes. Range of duration of IOP elevation was 20-362 days. There was no correlation between [glutamate] and axon count, IOP, C/D ratio, duration of IOP elevation, or age. Conclusion: Past reports have suggested that glutamate might play a role in excitotoxicity and apoptosis in retinal ganglion cells in glaucoma. In our data set, there was no clear-cut difference between vitreous glutamate concentration in glaucomatous and contralateral control monkey eyes. Further analyses and experiments are planned to resolve outstanding questions, such as whether additional variables (e.g., duration of sample storage, ocular hypotensive drug therapy) might have affected the findings.
Keywords: 402 excitatory neurotransmitters • 316 animal model • 629 vitreous