Prevention of posterior capsular opacification throughcyclooxygenase-2 inhibition

[摘要] Purpose: To determine if cyclooxygenase-2 (COX-2) is upregulatedwhen lens epithelial cells (LEC) in clinical samples of cataracts andposterior capsule opacification (PCO) undergo epithelial-mesenchymaltransition (EMT)-like changes. We also wanted to learn if inhibition ofthe enzymatic activity of COX-2 could prevent PCO formation.Methods: To ensure that EMT-like changes were occurring in LEC,real-time RT-PCR was used to examine expression of EMT markers. Clinicalsamples of canine cataracts and PCO were examined for COX-2 expressionusing immunohistochemistry, western blot analysis, and real-time RT-PCR.The COX-2 inhibitors, rofecoxib and celecoxib, were used in an ex vivomodel of PCO formation, and the effects on cellular migration,proliferation, and apoptosis were analyzed using immunohistochemistryand western blots. Prostaglandin E2 (PGE2) expression was examined withELISA.Results: Markers of EMT, such as lumican, Snail, Slug, and COX-2were expressed in LEC. In clinical samples of cataracts and PCO, therewas overexpression of COX-2 protein and mRNA. Both rofecoxib andcelecoxib were effective at inhibiting PCO formation in our ex vivomodel. Prevention of PCO with the COX-2 inhibitors appeared to workthrough decreased migration and proliferation, and increased apoptosis.Neither of the drugs had a toxic effect on confluent LEC and appeared toinhibit PCO through their pharmacologic action. Synthesis of PGE2 wasinhibiting in the capsules treated with the COX-2 inhibiting drugs.Conclusions: Extracapsular phacoemulsification cataract surgery isthe most common surgical procedure performed in human and veterinaryophthalmology. The most frequent postoperative complication is PCO. TheLEC that remain adhered to the lens capsule undergo EMT-like changes,proliferate, and migrate across the posterior lens capsule causingopacities. We have shown that COX-2, a protein associated with EMT, isupregulated in canine cataracts and PCO. Inhibiting the enzymaticactivity effectively prevented EMT of LEC in our ex vivo model of PCOthrough pharmacologic action, and not acute toxicity. These findingsindicate that using COX-2 inhibitors in vivo may be an effectivetechnique in preventing PCO.

[学科分类] 生物化学/生物物理