Abstract
Purpose :
The purpose of this study was to evaluate the efficacy of monocular and bilateral injections of Dexamethasone-21-acetate (Dex-21-Ac) into the murine fornix twice a week as a glucocorticoid-induced ocular hypertension model, as well as to explore potential systemic adverse effects.
Methods :
Three groups were examined: 1) bilateral injections with Dex-21-Ac, 2) monocular injections with Dex-21-Ac, 3) control group that received the vehicle solution bilaterally. Enucleated eyes were evaluated using immunocytochemistry (ICC) after 21 days, additionally organ histology was performed.
Results :
Intraocular pressure (IOP) increased significantly in both groups that received Dex-21-Ac injections. A significant rise in IOP from 14.12 mmHg (SEM: 0.73, n=7) to 22.56 mmHg (SEM: 0.75, n=4) at the end of the experiment was observed in the monocular injection group. The IOP also increased in the fellow eye from 14.24 mmHg (SEM: 0.59, n=7) to 21.31 mmHg (SEM: 1.48, n=4). Similarly, the group receiving binocular Dex-21-Ac injections exhibited a significant increase in IOP from 14.35 mmHg (SEM: 0.49, n=10) to 21.29 mmHg (SEM: 0.64, n=6). This rise in IOP was accompanied by an increase in alpha smooth muscle actin and fibronectin expression in the anterior chamber angle. No significant changes in animal weight were observed. Hepatic steatosis was found in all Dex-21-Ac-treated animals, and three of them showed residual neuromuscular blockade while under fentanyl anesthesia.
Conclusions :
Bilateral Dex-21-Ac injections twice a week cause a considerable rise in daytime IOP as well as fibrotic alterations in the trabecular meshwork. Unilateral application has a significant impact on the fellow eye. Local dexamethasone causes significant systemic effects that do not correlate with changes in animal weight. Due to the potential for liver damage caused by Dex-21-Ac and its impact on metabolism, hepatically eliminated injection anesthetics could result in overdosing and are therefore not advised. We recommend using inhalation anesthesia in this model instead.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.