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Ultrastructural effects of topical beta-adrenergic antagonists and an alpha-adrenergic agonist on the rabbit cornea
1Department of Histology and Embryology, University of Cukurova Medical Faculty, Adana, Turkey.
Abstract:
In the present study the effects of beta-adrenergic antagonist and alpha-adrenergic agonist drugs on rabbit corneas were evaluated in vivo by using transmission electron microscopy. Twenty-four New Zealand albino rabbits were divided into six groups according to the drug applied. The rabbits to which only balanced salt solution (BSS) or BSS and benzalkonium chloride (BAC) were applied were taken as the control groups. The other four groups consisted of the rabbits to which Timoptic 0.5%, Betagan 0.5%, Betoptic 0.5% and Iopidine 1% were applied, respectively. All of drugs were instilled topically twice daily for 6 weeks. In the BSS group, all layers of the cornea were ultrastructurally normal. In the BSS and BAC group slight epithelial and endothelial changes were found. However, in the other groups, loss of microvilli, increase in glycogen particles, nuclear indentation, widening of the intercellular spaces and cytoplasmic vacuolization in epithelium were observed. No significant abnormality was found in the basal lamina, stroma and Descemet's membrane. Slight ultrastructural changes were noted in the endothelium such as vacuolization due to dilatation of the endoplasmic reticulum cisternae and focal cytoplasmic lytic areas. The results of this study indicate that various ultrastructural changes occur in groups treated with antiglaucomatous drug and that topical treatment with timolol and apraclonidine for 6 weeks is more toxic to the rabbit cornea than levobunolol and betaxolol.
Insights
Topical antiglaucoma drugs like timolol and apraclonidine caused more rabbit corneal ultrastructural changes than levobunolol and betaxolol over six weeks. These findings highlight potential toxicity concerns for specific glaucoma treatments.
Area of Science:
- Ophthalmology
- Pharmacology
- Cell Biology
Background:
- Glaucoma treatment often involves topical medications.
- Understanding the ocular surface toxicity of these drugs is crucial for patient safety.
- Beta-adrenergic antagonists and alpha-adrenergic agonists are common classes of antiglaucoma drugs.
Purpose of the Study:
- To evaluate the in vivo effects of specific beta-adrenergic antagonist and alpha-adrenergic agonist drugs on rabbit corneas.
- To compare the ultrastructural toxicity of timolol, levobunolol, betaxolol, and apraclonidine on the cornea.
- To assess corneal changes after 6 weeks of topical drug instillation.
Main Methods:
- Twenty-four New Zealand albino rabbits were used.
- Corneas were treated topically twice daily for 6 weeks with balanced salt solution (BSS), BSS with benzalkonium chloride (BAC), Timoptic 0.5%, Betagan 0.5%, Betoptic 0.5%, or Iopidine 1%.
- Transmission electron microscopy was employed to examine corneal ultrastructure.
Main Results:
- BSS group showed normal corneal ultrastructure.
- BSS and BAC group exhibited slight epithelial and endothelial changes.
- Groups treated with Timoptic (timolol), Betagan (levobunolol), Betoptic (betaxolol), and Iopidine (apraclonidine) showed epithelial alterations including loss of microvilli, increased glycogen, nuclear indentation, intercellular widening, and cytoplasmic vacuolization.
- Endothelial changes included vacuolization and focal cytoplasmic lysis.
- Basal lamina, stroma, and Descemet's membrane remained largely unaffected.
- Timolol and apraclonidine demonstrated greater corneal toxicity compared to levobunolol and betaxolol.
Conclusions:
- Topical antiglaucoma medications can induce significant ultrastructural changes in the rabbit cornea.
- Timolol and apraclonidine appear to be more toxic to the rabbit cornea than levobunolol and betaxolol following 6 weeks of topical application.
- These findings underscore the importance of considering drug-induced corneal toxicity in glaucoma management.