Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice

Int J Mol Sci. 2021 Oct 28;22(21):11670. doi: 10.3390/ijms222111670.

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.

Keywords: doxycycline; proliferative vitreoretinopathy (PVR); rhegmatogenous retinal detachment (RRD).

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Cell Line
  • Chemokine CXCL9 / metabolism
  • Doxycycline / administration & dosage*
  • Drug Evaluation, Preclinical
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Intravitreal Injections
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Retina / drug effects
  • Retina / enzymology
  • Vitreoretinopathy, Proliferative / drug therapy*
  • Vitreoretinopathy, Proliferative / metabolism
  • Vitreous Body / drug effects
  • Vitreous Body / enzymology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Bacterial Agents
  • Chemokine CXCL9
  • Cxcl9 protein, mouse
  • IL10 protein, mouse
  • Il4 protein, mouse
  • Interleukin-10
  • Interleukin-4
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Doxycycline