Evaluation of glutamate loss from damaged retinal cells of dogs with primary glaucoma.
OBJECTIVE
To determine whether retinal damage in dogs with primary glaucoma (PG) is consistent with ischemia-induced glutamate toxicosis.


METHODS
Retinal tissue sections from 25 dogs with PG and 12 normotensive control dogs.


METHODS
Retinal sections from control and glaucomatous dogs were stained for morphometric and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analyses to determine whether retinal damage was consistent with glutamate toxicosis. Immunohistochemical analysis was performed to detect ischemia-like loss of glutamate from neurons in damaged areas.


RESULTS
In severely damaged glaucomatous retinas, all neurosensory layers had focal regions that were thin or disrupted. There was less thinning of the outer nuclear layer (ONL) and inner nuclear layer (INL) in moderately damaged retinas than in severely damaged retinas. Acute signs of damage in the INL included cells with dark, condensed chromatin and lightly stained cytoplasm interspersed with a few TUNEL-positive cells, which was consistent with glutamate toxicosis. Glutamate immunoreactivity was reduced in thin areas and in damaged cells of the INL and ONL, which was consistent with glutamate release in damaged areas. Glutamate immunoreactivity was increased in putative Müller cells in damaged areas, which also was consistent with glutamate release.


CONCLUSIONS
Retinal damage in dogs with PG differs in intensity in focal areas. Damage in affected regions resembles damage induced by glutamate. Glutamate is lost from damaged neurons and accumulates in Müller cells, which is consistent with increased glutamate release contributing to the damage. Glutamate antagonists may protect INL cells in dogs with glaucoma.
McIlnay
Tonya R
TR
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-7051, USA.
Gionfriddo
Juliet R
JR
Dubielzig
Richard R
RR
Powell
Cynthia C
CC
Madl
James E
JE
D000704:Analysis of Variance; D000818:Animals; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D018698:Glutamic Acid