Topical ocular dexamethasone decreases intraocular pressure and body weight in rats

Recently, topical dexamethasone-induced ocular hypertension and a consequent loss of retinal ganglion cells (RGCs) have been described in mice. This has been proposed as a model of steroid-induced glaucoma. In this study, we set up and evaluated a similar model in rats.

Ten-week old Sprague Dawley (SD) rats (N = 12) were used to evaluate the effect of topical 0.1% dexamethasone (50 μl) administered 3 times daily for 4 weeks. Sodium chloride (0.9%) was used in another group of rats (N = 12) that served as the controls. After 1 week, we observed a progressive decrease in body weight in the dexamethasone-treated rats compared both to the pre-treatment baseline and the vehicle-treated rats. In contrast to earlier work that showed elevated Intraocular pressure (IOP) following dexamethasone instillation in mice, IOP in the rats unexpectedly fell to 11.3 ± 1.3 mmHg in the treated eyes, compared to 14.8 ± 2.4 mmHg in the untreated eyes, after 3 weeks of topical dexamethasone (P = 0.032). Blood tests performed after 4 weeks of treatment showed a 3.3-fold increase in both plasma cholesterol (P < 0.001) and alanine transaminase (P = 0.019) in the dexamethasone-treated rats compared to the control rats. Meanwhile, topical steroid did not induce changes in either plasma blood glucose or glycated hemoglobin (HbA1c). We also did not detect changes in the expression of RGC markers (with real-time PCR) following the treatment.

In contrast to mice, which previously showed increased IOP following the topical administration of dexamethasone, the rats displayed a paradoxical reduction in IOP following a similar treatment. This was accompanied by a loss of body weight without affecting the level of blood glucose.