Model systems for the study of steroid-induced IOP elevation

Abstract

Steroid-induced IOP elevation affects a significant number of patients. It results from a decrease in outflow facility of the aqueous humor. To understand the pathophysiology of this condition a number of model systems have been created. These include ex-vivo cell and organ cultures as well as in-vivo animal models in organisms ranging from rodents to primates. These model systems can be used to investigate specific aspects of steroid-induced IOP elevation. This brief review summarizes the strengths and limitations of the various model systems and provides examples of where these systems have been successfully used to advance our understanding of steroid-induced IOP elevation.

Keywords: Glaucoma; Intraocular pressure; Model; Steroids.

Figure 1

Topical and intracameral tPA reduces IOP in steroid-induced ocular hypertensive sheep. 4 mg of lyophilized tPA (Actilyse^®, Boehringer Ingelheim SA BuenosAires, Argentina) were dissolved in 0.4 mL artificial tears (Refresh Plus). Because tPA is formulated with arginine (43.3mg per mg of tPA) an equivalent amount of arginine was dissolved in artificial tears and was used as control. Eyes of 6 sheep received topical application of tPA (N=6 eyes) or vehicle control (N=4 eyes)) at time 0h. Some eyes (AC injection − N=2) received 10ug of tPA intracamerally in 50ul of balanced salt solution 2-3h prior to time 0h. All eyes had been treated with steroids topically (two drops of 1.0% prednisolone acetate (Alcon, Fort Worth, Texas) 3-times daily (7AM, 2PM, and 7PM) for 8 days) to induce IOP elevation (baseline IOP prior to steroid induced IOP elevation was 11.3 ± 0.2 mmHg). Treatment with steroids continued for the duration of the experiment. Error bars indicate standard deviation of measurements. Statistically significant differences (p<0.05, ANOVA) are indicated by an asterisk (*). Arrow indicate the points of administration of tPA topically (green arrow) or intracamerally (blue arrow).