Original article
A Rat Model for Acute Rise in Intraocular Pressure: Immune Modulation as a Therapeutic Strategy

https://doi.org/10.1016/j.ajo.2006.01.073Get rights and content

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.

Section snippets

Animals

Inbred adult male Lewis rats (average weight 250 g, age eight weeks) were supplied by the Animal Breeding Center at the Weizmann Institute of Science. The rats were raised in a light- and temperature-controlled room and were matched for age and weight before each experiment. All animals were handled according to the regulations formulated by the International Animal Care and Use Committee (IACUC) and the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Institutional

Induction of an acute increase in intraocular pressure in rats

Saline infusion to the rats’ anterior chamber caused IOP rise to 100 cm H2O; this was equal to the height of the infusion bag. Twenty-four hours after elevation, the mean IOP had returned to normal (19 ± 4 mm Hg).

Loss of retinal ganglion cells caused by acute increase in intraocular pressure

To investigate the effect of IOP on RGC survival we examined three groups of rats. Rats in group 1 (n = 6), which served as a control, were not subjected to an increase in IOP. Rats in group 2 (n = 14) and group 3 (n = 12) were subjected for one hour to an IOP insult, as described

Discussion

In the rat model of acute rise in IOP described here, the increase in pressure was controlled, transient, and reproducible. Since there was no evidence of other damage in these eyes, the loss of RGCs can be assumed to be caused solely by the acute increase in IOP; loss of RGCs is amenable to neuroprotective therapy.

An acute increase in IOP in the eyes of experimental animals can also be induced by pharmacological and surgical interventions.2, 3, 4, 5, 6, 7, 28 All of these methods, however, are

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  • Cited by (0)

    The authors thank Michal Schwartz, PhD, and Larry Wheeler, PhD, for their assistance in study design, analyzing and interpreting the results, and critical review of the manuscript.

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