A rat model for acute rise in intraocular pressure: immune modulation as a therapeutic strategy.
OBJECTIVE
To establish a rat model of acute increase in intraocular pressure (IOP) and to investigate the therapeutic window for protection against death of retinal ganglion cells (RGCs) by vaccination with glatiramer acetate (Cop-1) or by treatment with brimonidine or MK-801.


METHODS
Animal study, laboratory investigation.


METHODS
IOP was transiently increased in anesthetized Lewis rats by infusing normal saline (0.9%) into the anterior chamber of the eye for one hour. RGC survival was assessed one week and two weeks later by counting the RGCs retrogradely labeled with rhodamine dextran.


METHODS
RGC survival.


RESULTS
IOP rose to 100 cm H(2)O (76 mm Hg) and returned to baseline after 24 hours. The RGC count decreased by 23% a week after the insult and by a further 7% after the second week. Vaccination with Cop-1 on the day of the insult prevented 50% of the IOP-induced RGC loss. Similar neuroprotection was achieved by daily intraperitoneal injections of brimonidine, but not with MK-801.


CONCLUSIONS
A transient increase in IOP to 100 cm H(2)O causes death of RGCs in rats. A single immunization with Cop-1 or daily injections of brimonidine protected up to 50% of potentially doomed RGCs from IOP-induced death, suggesting that not all of the cell death in the untreated model results from the IOP insult directly, but that some of it is caused by insult-induced environmental cytotoxicity, which is unrelated to glutamate toxicity or at least to NMDA receptors. These findings can be applied immediately as a basis for acute glaucoma therapy.
Ben Simon
Guy J
GJ
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel. guybensimon@gmail.com
Bakalash
Sharon
S
Aloni
Eyal
E
Rosner
Mordechai
M
D000208:Acute Disease; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000068438:Brimonidine Tartrate; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D000068717:Glatiramer Acetate; D007114:Immunization; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009798:Ocular Hypertension / Q000150:complications / Q000188:drug therapy*; D009901:Optic Nerve Diseases / Q000188:drug therapy / Q000209:etiology; D010455:Peptides / Q000008:administration & dosage*; D011810:Quinoxalines / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014611:Vaccination
D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D010455:Peptides; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D000068717:Glatiramer Acetate; D016291:Dizocilpine Maleate