The Effect of Phosphorylated Akt Inhibition on Posterior Capsular Opacification in the Canine Lens

Abstract

Abstract: : Purpose: To test the importance of phosphorylated Akt (pAkt) during formation of posterior capsular opacificaton (PCO) after cataract surgery. Our collaborators have developed a celecoxib–derivative, OSU03012 that has enhanced pAkt inhibition and abolished capacity to inhibit COX2. We have previously shown that pAKT is overexpressed in lens bags with PCO versus normal lenses, as well as in clinical samples of PCO. We hypothesize that this chemical will inhibit pAkt in lens epithelial cells (LEC) and prevent the formation of PCO. Methods: To determine chemical toxicity of OSU03012on LEC, cultures were incubated with various doses of the pAkt inhibitor. From this, we determined the treatment doses would be 0, 2.5, 5, 7.5, 10µM. Lens capsules were harvested post–sham cataract surgery. The capsules were treated with OSU03012in serum free media. Media and chemical were replaced every 3 days for a total of 2 weeks of treatment. Digital photographs and histopathology were performed to evaluate PCO formation. Results: Within the region of the capsulorrhexis, PCO inhibition was achieved with 5, 7.5, and 10µM of chemical, which was evident on digital photographs and histopathology of lens bags. Conclusions: pAkt is known to have roles in cell survival, proliferation, and migration, and preliminary data suggests its importance in PCO formation. There was no proliferation or migration of LEC onto the posterior lens capsule of the lens bag. This suggests that the pAkt inhibitory effects of the chemical prevented PCO formation. Future studies aim to clarify the mechanisms by which this inhibition of migration and proliferation is occurring.

Keywords: posterior capsular opacification (PCO) • cataract