Regulation and mechanism of chloride channels in proliferative vitreoretinopathy

This study aimed to investigate the regulation of chloride channels in proliferative vitreoretinopathy (PVR) both in vitro and in vivo using a rabbit model and to explore the underlying mechanism.

The chloride channel is regulated by the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and the chloride channel activator lubiprostone. CCK-8, cell scratch, and Transwell assays assessed retinal pigment epithelium (RPE) cell proliferation and migration. Changes in the expression of the extracellular matrix proteins CollagenI, CollagenIII, fibronectin and α-SMA in ARPE19 cells were detected by Western blotting. In the in vivo study, NPPB or lubiprostone was injected intravitreally after the PVR model was established. The degree of traumatic PVR was evaluated and graded by observing the structures of the anterior segment, vitreous body, and fundus in rabbits.

Lubiprostone promoted transforming growth factor-β1 induced ARPE 19 cell growth and invasion, thereby facilitating PVR formation. In contrast, NPPB had the opposite effect, as it inhibited PVR formation. Consistent results were also observed in in vivo models. A novel therapeutic approach for treating PVR, which is based on chloride channels, was explored.

By reducing the opening of chloride channels within RPE cells via drugs, PVR formation can be suppressed, which is sufficient to counteract retinal degeneration. Chloride channels may have crucial effects on RPE cell proliferation and migration. The therapeutic strategy of blocking chloride channels may be beneficial for PVR.