TY - JOUR
T1 - A Rat Model for Acute Rise in Intraocular Pressure
T2 - Immune Modulation as a Therapeutic Strategy
AU - Ben Simon, Guy J.
AU - Bakalash, Sharon
AU - Aloni, Eyal
AU - Rosner, Mordechai
PY - 2006/6
Y1 - 2006/6
N2 - Purpose: 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. Design: 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. main outcome measures: RGC survival. Results: IOP rose to 100 cm H2O (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 H2O 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.
AB - Purpose: 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. Design: 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. main outcome measures: RGC survival. Results: IOP rose to 100 cm H2O (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 H2O 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.
UR - http://www.scopus.com/inward/record.url?scp=33744790311&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2006.01.073
DO - 10.1016/j.ajo.2006.01.073
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C2 - 16765680
AN - SCOPUS:33744790311
SN - 0002-9394
VL - 141
SP - 1105
EP - 1111
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
IS - 6
ER -