Drug-Induced Secondary Cataract Prevention: Experimental ex vivo and in vivo Results with Disulfiram, Methotrexate and Actinomycin D

Abstract

Background/Aims: 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.

Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment

“…For the presented application HA was chosen, since HA is commonly used in addition to cellulose derivatives as a viscoelastic biomaterial for routine cataract surgery, serving to stabilize the anterior chamber. Furthermore, the potential of HA loaded with antiproliferative model drugs was studied regarding the effectiveness of local drug delivery for lens epithelial cell ablation from the basal membrane and for prevention of secondary cataract formation [39]. However, in that study pure, non-crosslinked hydrogel was used, as only 2-5 minutes of drug release were needed.…”

The Risk of Cataract among Survivors of Childhood and Adolescent Cancer: A Report from the Childhood Cancer Survivor Study

“…The results from the current study also indicate that use of methotrexate was associated with a lower incidence of cataract independent of radiotherapy. Treating lens epithelial cells with methotrexate and actinomycin D proved to be an effective method for preventing posterior capsule opacification in rabbits (36). In a retrospective cohort study of children with juvenile idiopathic arthritis-associated uveitis, it was also reported that there was a significantly lower risk of cataract surgery over time in patients treated with methotrexate (37).…”

In vivo 7.1 T magnetic resonance imaging to assess the lens geometry in rabbit eyes 3 years after lens-refilling surgery

“…Based on previous experimental results, 13 an OVD mixture containing actinomycin D plus DL-methotrexate embedded in sodium hyaluronate was chosen to prevent secondary cataract formation. In rabbits, DL-methotrexate (mean molecular weight 454.4 g/mol) and actinomycin D (mean molecular weight 1,255.4 g/mol) were obtained from Sigma-Aldrich Chemie GmbH.…”