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Understanding the Ocular Hypertension Model in Mice Induced by Dexamethasone-21-Acetate - Implications for Glaucoma
Maximilian Binter1, Miriam Heider2, Silke Glage2
1Department of Ophthalmology, University Eye Hospital, Hannover Medical School, Hannover, Germany.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Bilateral injections of Dexamethasone-21-acetate (Dex-21-Ac) increase intraocular pressure (IOP) and cause fibrotic changes. Unilateral injections impact the fellow eye, and systemic effects like liver damage occur, necessitating anesthesia changes.
Area of Science:
- Ophthalmology
- Pharmacology
- Toxicology
Background:
- Glucocorticoids are widely used for ocular inflammation.
- Dexamethasone-induced ocular hypertension is a common animal model.
- Understanding systemic side effects is crucial for safe clinical application.
Purpose of the Study:
- To evaluate Dexamethasone-21-acetate (Dex-21-Ac) as a glucocorticoid-induced ocular hypertension model in mice.
- To assess the effectiveness of monocular versus bilateral Dex-21-Ac injections.
- To investigate potential systemic side effects of Dex-21-Ac administration.
Main Methods:
- Mice received bilateral or monocular injections of Dex-21-Ac or vehicle twice weekly for 21 days.
- Intraocular pressure (IOP) was measured.
- Immunocytochemistry and organ histology were performed on enucleated eyes.
Main Results:
- Dex-21-Ac injections significantly increased IOP bilaterally (approx. 8 mmHg).
- Monocular injections also elevated IOP in the fellow eye.
- Elevated alpha-smooth muscle actin and fibronectin were observed in the anterior chamber angle.
- Hepatic steatosis occurred in all treated animals; some experienced neuromuscular blockade under fentanyl anesthesia.
Conclusions:
- Bilateral Dex-21-Ac injections effectively model ocular hypertension with fibrotic changes.
- Unilateral injections have a significant effect on the contralateral eye.
- Systemic effects, including liver damage, are independent of weight changes.
- Caution is advised with hepatically eliminated anesthetics; inhalation anesthesia is recommended.
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