Vitreous Glutamate Concentration and Axon Loss in Monkeys With Experimental Glaucoma

Abstract

To evaluate vitreous glutamate concentration and axon loss in monkeys with experimental glaucoma.Methods : We induced unilateral chronic glaucoma by means of laser trabecular destruction in 14 rhesus and 6 cynomolgus monkeys. Intraocular pressure (IOP) was monitored weekly. We assessed optic nerve damage clinically and photographically. Vitreous, sampled immediately before enucleation, was analyzed for glutamate concentration by means of high-performance liquid chromatography. We quantified percentage of axon loss after histopathologic sectioning of the optic nerve, compared median glutamate concentration ratios, and assessed correlation of glutamate concentration, axon count, IOP, cup-disc ratio, duration of IOP elevation, and age.Results: Median vitreous glutamate concentration in glaucomatous eyes was 7.0 µmol/L (range, 3.0-88.6 µmol/L) vs 6.7 µmol/L (range, 2.8-87.4 µmol/L) in control eyes. The ratio (glaucomatous to control eyes) was 1.08. We found no significant correlation between vitreous glutamate concentration ratio and any of the other variables. The IOP, disc cupping, and axon loss were correlated. Conclusions:We found no difference between vitreous glutamate concentration in glaucomatous and contralateral control monkey eyes when the entire data set was examined and no evidence of correlation between vitreous glutamate concentration and axon loss.

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

“…Although the literature reports conflicting data (Dreyer et al, 1996: Brooks et al, 1997Levkovitch-Verbin et al, 2002;CarterDawson et al, 2002;Honkanen et al, 2003;Wamsley et al, 2005), increased vitreal glutamate concentrations have been demonstrated in experimental models of glaucoma (Louzada-Júnior et al, 1992;Adachi et al, 1998;Nucci et al, 2005b) and this can be associated with excitatory amino acid transporters (EEAT) dysfunction Russo et al, 2013b).…”

Excitotoxicity Upregulates SARM1 Protein Expression and Promotes Wallerian-Like Degeneration of Retinal Ganglion Cells and Their Axons

“…[1][2][3] Despite the fact that the elevated IOP has been identified as a risk factor for the degeneration of RGCs in glaucoma, the mechanisms underlying IOP-mediated retinal damage are still unclear. A number of hypotheses have been proposed, including alterations in transport of neurotropic factors, 4,5 retinal ischemia, 6,7 increase in endothelial nitric oxide synthase (eNOS), 8,9 reactive gliosis, 9 excitotoxicity, 10,11 and axonal self-destruction. 12 Among these hypotheses, evidence regarding the role of glutamate in RGC death has been controversial, and, to date, the role of increased levels of glutamate in RGC death in glaucomatous damage has never been substantiated.…”

Neuroprotection in Glaucoma

“…Another study found 5-fold higher levels of glutamate in dogs with primary glaucoma, compared with normal dogs. However two subsequent studies carried out in primates found no significant increase in vitreal glutamate in IOP elevated monkey eyes, compared to those in control eyes (Carter-Dawson et al, 2002;Wamsley et al, 2005). It is possible that the confounding factors such as increased activity of EAATs in glial cells that could be masking the increased glutamate concentrations that may occur in a narrow time window following ocular hypertension.…”