Abstract

After successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of the epiretinal membrane, while effective treatment to prevent PVR is still unavailable. Therefore, we investigated the potential of doxycycline, an antibiotic in the tetracycline class, to treat PVR using a mouse model. We used the human retinal pigment epithelial cell line, ARPE-19, for in vitro and in vivo studies to test doxycycline for PVR treatment. We found that doxycycline suppressed the migration, proliferation, and contraction of ARPE-19 cells with reduced p38 MAPK activation and total MMP activity. Intravitreal doxycycline and topical tetracycline treatment significantly ameliorated the PVR severity induced by ARPE-19 cells in mice. PVR increased the expression of MMP-9 and IL-4 and p38 MAPK phosphorylation and modestly decreased IL-10. These effects were reversed by doxycycline and tetracycline treatment in the mouse retina. These results suggest that doxycycline will be a potential treatment for PVR in the future.

Highlights

  • Published: 28 October 2021Rhegmatogenous retinal detachment (RRD) is a severe and potential sight-threatening disease

  • The primary surgical reattachment rate of RRD is from 75% to 90%, but around 10% of initially successful cases result in retinal redetachment due to proliferative vitreoretinopathy (PVR) [5,6,7,8], which is the most common cause of failed repair of RRD [1,5,9]

  • We evaluated whether doxycycline can reduce the proliferation of ARPE-19 cells, which proliferated after culture (Figure 1B)

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Summary

Introduction

Rhegmatogenous retinal detachment (RRD) is a severe and potential sight-threatening disease. The annual incidence of RRD is between 5.4 and 18.2 per 100,000 people [1,2,3,4]. The primary surgical reattachment rate of RRD is from 75% to 90%, but around 10% of initially successful cases result in retinal redetachment due to proliferative vitreoretinopathy (PVR) [5,6,7,8], which is the most common cause of failed repair of RRD [1,5,9]. The surgical success rate for PVR is approximately 60–75% at 6 months, and more than 25% of initially successful cases result in retinal redetachment due to recurrent retinal traction [1]. PVR is the result of the growth and contraction of cellular membranes within the hyaloid and retinal surface

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