Abstract
Purpose :
Posterior capsule opacification (PCO) is a common complication of cataract surgery. HSP90 chaperone complex regulates cellular proteostasis during cell proliferation and differentiation at both physiological and pathological conditions. Here we test the hypothesis that HSP90 plays a prominent role in regulating PCO formation and maybe a novel therapeutic target for PCO.
Methods :
2 months old Wistar rat lens capsular bags cultured ex vivo or capsular residual cell expansion assay in vitro were used for the mimetic PCO process. The cell proliferation was tested by MTT and EdU staining. The cell apoptosis was assessed by TUNEL and activation of Caspase 3. The protein expression and protein-protein interaction were tested by immunoblotting, immunoprecipitation and immunofluorescent staining.
Results :
HSP90 expresses constitutively in the tested mouse and human lens epithelial cell lines, and HSP90 inhibitor 17-AAG inhibits the cells’ growth. In the ex vivo cultured lens capsular bags, 65% of the capsular residual cells are EdU positive at 24hrs post-capsulorhexis. The cells take about 3-6 days to completely overlay the capsular posterior walls. HSP90, EGFR, P-ERK1/2 and p-AKT are induced in the lens capsular residual cells. 17-AAG reduces EGFR protein stability and inhibits the activities of ERK1/2 and AKT. In addition, 17-AAG upregulates ROS level and cytosolic release of cytochrome C and induces the apoptosis of capsular residual cells. No cytotoxicity of 17-AAG on corneal cells was observed.
Conclusions :
HSP90 is induced and regulates capsular residual cells survival and proliferation by in part associating with EGFR pathway during PCO formation. 17-AAG, which is specifically toxic to capsule residual cells, is the potential therapeutic candidates for PCO prevention
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.