Understanding the Ocular Hypertension Model in Mice Induced by Dexamethasone-21-Acetate - Implications for Glaucoma Research

• Published in: Current eye research 2024-12, Vol.49 (12), p.1269-9
• Main Authors: Binter, Maximilian, Heider, Miriam, Glage, Silke, Fuchs, Heiko, Langer, Fridolin, Schigiel, Thomas, Framme, Carsten, Tode, Jan
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Dexamethasone - analogs & derivatives; Dexamethasone - toxicity; Disease Models, Animal; Fibronectins - metabolism; Glaucoma - drug therapy; Glaucoma - physiopathology; Glucocorticoids - toxicity; Immunohistochemistry; Intraocular Pressure - drug effects; Male; Mice; Mice, Inbred C57BL; Ocular Hypertension - chemically induced; Ocular Hypertension - drug therapy; Ocular Hypertension - physiopathology; Tonometry, Ocular
• ISSN: 0271-3683; 1460-2202; 1460-2202
• DOI: 10.1080/02713683.2024.2380445

This study aimed to assess the effectiveness 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 and investigated potential systemic side effects. Dex-21-Ac was administered twice weekly in three groups: bilateral injections, monocular injections, and a control group receiving the vehicle solution bilateral. After 21 days, enucleated eyes were examined using immunocytochemistry (ICC), and organ histology was performed. All groups receiving Dex-21-Ac injections had a significant increase in intraocular pressure (IOP). Monocular injections also resulted in a significant increase in IOP in the fellow eye. The Dex-21-Ac-treated groups showed a bilateral increase in IOP of approximately 8 mmHg, accompanied by elevated expression of alpha smooth muscle actin and fibronectin in the anterior chamber angle. There were no significant changes in weight progression. Hepatic steatosis was observed in all Dex-21-Ac-treated animals, and some suffered from residual neuromuscular blockade under fentanyl anesthesia. Bilateral injections of Dex-21-Ac twice a week lead to a significant increase in daytime IOP and fibrotic changes in the trabecular meshwork. Unilateral application has a significant impact on the fellow eye. Local dexamethasone leads to notable systemic effects independent of changes in animal weight. Considering liver damage and associated influence on metabolization, hepatically eliminated injection anesthetics may lead to overdosing and are not recommended. They should be replaced by inhalation anesthesia.