Loss of glutamine synthetase in the retina of dogs

Abstract

PURPOSE: Changes in retinal glutamate distribution occur in primary glaucoma (PG) in dogs. Although the redistribution resembles that induced by ischemia, decreases in glutamine synthetase (GS) activity may also induce a similar glutamate redistribution. We examined the distribution of GS, glutamate, and glial fibrillary acidic protein (GFAP), a marker for reactive glia, in PG retinas by immunohistochemistry to determine whether decreases in GS and formation of reactive glia are associated with glutamate redistribution and neuronal damage. ANIMALS: Sections from 14 control dog eyes and 22 eyes from dogs with PG. METHODS: Sections from 14 control and 22 glaucomatous globes were immunohistochemically stained for GS, glial fibrillary acidic protein or glutamate. RESULTS: In semiquantitative immunogold studies, decreases in GS staining density were strongly correlated with glutamate redistribution and neuronal damage. In less quantitative immunoperoxidase staining of acute (< or = 5 days after clinical signs) and chronic PG retinas, GS immunoreactivity was decreased in focal regions of some acute PG retinas, and there were widespread decreases in chronic PG retinas. GFAP immunoreactivity was increased in M&#xfc;ller cells primarily in severely damaged regions of chronic PG retinas. CONCLUSIONS: Decreases in GS immunoreactivity were associated with glutamate redistribution. These decreases in GS occurred even in mildly damaged regions of retina before retinal thinning. Reactive M&#xfc;ller cells were seen primarily in chronic PG in severely damaged regions. Decreases in GS may potentiate ischemia-induced early glutamate redistribution and neuronal damage in canine PG.