Drug-induced secondary cataract prevention: experimental ex vivo and in vivo results with disulfiram, methotrexate and actinomycin D.
OBJECTIVE
A clinical approach to prevent secondary cataract after lens implantation involves the intraocular application of pharmacological agents. The goals of our study were to develop an ex vivo model to test the drug effectiveness for lens epithelial cell ablation from the basal membrane and to verify the data in rabbit intraocular lens implantation experiments.


METHODS
Human capsular rhexis specimens were incubated with drugs and the residual cells were differentiated by use of the Live-Dead assay and quantified by staining with Hoechst dye. After phakoemulsification of rabbit eyes and before intraocular lens implantation, capsular bags were filled with drug-loaded hyaluronic acid for 5 min.


RESULTS
An ex vivo model was established which allows the testing of drugs on lens epithelial cell ablation. Drug treatment reduced the number of viable cells on the specimens drastically, ranging between 0.44 ± 0.53% (6.0 ± 7.3 cells/mm²) for disulfiram, 0.27 ± 0.50% (3.7 ± 6.9 cells/mm²) for methotrexate and 0.07 ± 0.19% (0.1 ± 0.27 cells/mm²) for actinomycin D. Rabbit eyes treated with a mixture of methotrexate/actinomycin D showed no posterior capsule opacification at 4 months and a low opacification 6 months postoperatively. Without drug treatment low opacification starts 6 weeks postoperatively.


CONCLUSIONS
The drug screening in the described ex vivo model can help to reduce the number of preclinical studies for secondary cataract prevention. The successful ex vivo cell ablation by methotrexate/actinomycin D was confirmed by a delayed in vivo secondary cataract formation.
Sternberg
Katrin
K
Institute for Biomedical Engineering, University of Rostock, Rostock, Germany. katrin.sternberg@uni-rostock.de
Terwee
Thom
T
Stachs
Oliver
O
Guthoff
Rudolf
R
Löbler
Marian
M
Schmitz
Klaus-Peter
KP
D000818:Animals; D019923:Capsulorhexis; D002386:Cataract / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002452:Cell Count; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D006820:Hyaluronic Acid / Q000633:toxicity; D007903:Lens Capsule, Crystalline / Q000187:drug effects* / Q000473:pathology; D019654:Lens Implantation, Intraocular; D008727:Methotrexate / Q000494:pharmacology*; D023421:Models, Animal; D011183:Postoperative Complications / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits
D003609:Dactinomycin; D006820:Hyaluronic Acid; D004221:Disulfiram; D008727:Methotrexate