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.