Abstract
Purpose: :
To determine the effects of modified Cyclosporine A (CsA) on canine lens epithelial cell (LEC) and corneal endothelial cell viability in vitro.
Methods: :
Lens capsules and corneas were harvested from canine cadaver eyes. Using an ex vivo model of PCO, lens capsules were randomly assigned to one of three treatment groups: 0 µg/mL CsA (culture media only; n=6), 20 µg/mL CsA (n=9), or 40 µg/mL CsA (n=9) and were treated for 7 days before processing for routine H&E staining. Additional lens capsules were treated for 7 days with 0 µg/mL CsA (n=6) or 40 µg/mL CsA (n=6), subsequently incubated in culture media without CsA for 21 additional days, and were processed for routine H&E staining. Corneas (n=7 per group) were randomly assigned to one of three control groups (no treatment, BSS, mitomycin-C) or to one of three treatment groups (20, 40, 100 µg/mL CsA). Corneas were treated for 180 minutes prior to staining and histologic evaluation.
Results: :
Capsules that received culture media with no CsA had complete PCO formation by 7 days; capsules that were maintained for 28 days were wrinkled and confluent with LEC. Comparatively, capsules that received 20 µg/mL CsA had moderate LEC present by 7 days and capsules that received 40 µg/mL CsA had few to no LEC present by 7 days. Lens capsules initially treated with 40 µg/mL CsA and maintained for 28 days had progressive clearing of LEC without any regrowth by 28 days. Endothelial cell viability was not decreased in corneas acutely exposed to 20, 40, or 100 ug/mL of CsA, or in corneas from the negative control groups (no treatment or BSS). Endothelium acutely exposed to mitomycin-C (toxic control) was non-viable.
Conclusions: :
CsA results in decreased LEC viability in a dose-dependent fashion in vitro, with greater doses causing greater cytotoxicity. 40 ug/mL of CsA was most effective at clearing LEC and preventing long-term regrowth. CsA was not acutely toxic to the corneal endothelium at concentrations up to 100 ug/mL. CsA may be a safe and effective tool for the treatment of canine PCO.
Keywords: posterior capsular opacification (PCO) • drug toxicity/drug effects • cornea: endothelium