Carbonic anhydrase inhibitor alleviates retinal barrier toxicity in paclitaxel-induced retinopathy and macular edema by inhibiting CAXIV

Purpose To investigate the mechanism of paclitaxel (PTX)-induced macular edema and the therapeutic effect of carbonic anhydrase inhibitors (CAI) on this condition. Methods The effect of PTX on cell morphology was detected by immunofluorescence. Cell barrier was measured by measuring cell resistance across the epithelium. Western blotting analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to investigate the effects of PTX or PTX + CAI on the expression of carbonic anhydrase XIV ( CAXIV ), aquaporin 4 (AQP4) and inflammatory factors. After intraperitoneal injection of PTX in vivo, retinal electrophysiology (ERG) was used to evaluate the effects of drugs on visual electrophysiology. Results PTX inhibited the proliferation of ARPE-19 and Müller cells, promoting their apoptosis, changing their morphology and cell cycle, reducing the transepithelial resistance of ARPE-19 cells and promoting the expression of inflammatory factors; This process was alleviated after temporary withdrawal. CAI inhibited the upregulation of inflammatory factors. Following treatment with PTX, the expression levels of AQP4 and CAXIV were higher than control group; nevertheless, the levels of ZO-1 and OCLN were lower than control group. In vivo, the ERG analysis showed that the light- and dark-adapted 3.0 ERG, and dark-adapted 3.0 oscillatory potentials decreased to different degrees following treatment with PTX. Conclusion PTX-induced macular edema is mainly due to Müller cell toxicity. The condition can be alleviated by regulating water channels and enhancing subretinal fluid absorption. Thus, CAI may provide a new therapeutic approach for PTX-induced macular edema.