Ultrastructural effects of topical beta-adrenergic antagonists and an alpha-adrenergic agonist on the rabbit cornea

S Polat1, N Ozdemir, M Soylu

  • 1Department of Histology and Embryology, University of Cukurova Medical Faculty, Adana, Turkey.

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.

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