Pirfenidone ameliorates the formation of choroidal neovascularization in mice

Mol Med Rep. 2020 May;21(5):2162-2170. doi: 10.3892/mmr.2020.11007. Epub 2020 Feb 27.

Abstract

The formation and development of choroidal neovascularization (CNV) is accompanied by inflammation and fibrosis. Existing treatments are expensive and can cause irreversible complications. Pirfenidone (PFD) exerts anti‑inflammatory and anti‑fibrotic effects; however, its applications in the eye remain unclear. Male C57BL/6J mice (aged 6‑8 weeks) were used to explore whether PFD can inhibit the formation of laser‑induced CNV. The localization of transforming growth factor β2 (TGFβ2) was determined through immunofluorescent staining. After laser photocoagulation, the vehicle and PFD groups were intravitreally injected with 1 µl PBS and 1 µl 0.5% PFD, respectively. At day 7 after intravitreal injection, the expression of TGFβ2 and vascular endothelial growth factor (VEGF) was assessed. Fundus fluorescein angiography was performed to investigate the extent of fluorescence leakage, and the CNV areas were analyzed using a choroidal flat mount. The results demonstrated that, on day 7 after photocoagulation, the expression of TGFβ2 and VEGF was reduced in the experimental group. In addition, fluorescein angiography showed that the leakage area of CNV was significantly smaller in the PFD injection group than those observed in the control and vehicle groups. Moreover, the areas of CNV in the PFD injection group were smaller compared with those reported in the other two injection groups. Histopathological and TUNEL analyses performed on day 28 revealed that there were no notable abnormalities on the layers of the neural retina of PFD‑treated mice. In conclusion, intravitreal injection of PFD inhibited the formation of CNV in mice, likely via the downregulation of VEGF and TGFβ2, which did not cause damage to the mouse retina after 28 days of treatment.

Keywords: choroidal neovascularization; pirfenidone; transforming growth factor β2; vascular endothelial growth factor.

MeSH terms

  • Animals
  • Choroid / diagnostic imaging
  • Choroid / drug effects
  • Choroid / metabolism*
  • Choroid / pathology
  • Choroidal Neovascularization / diagnostic imaging
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / pathology*
  • Disease Models, Animal
  • Fluorescein Angiography
  • Fluorescent Antibody Technique
  • Intravitreal Injections
  • Lasers
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pyridones / therapeutic use*
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / radiation effects
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Pyridones
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • pirfenidone