Effects of kallidinogenase on retinal edema and size of non-perfused areas in mice with retinal vein occlusion

J Pharmacol Sci. 2017 Jun;134(2):86-92. doi: 10.1016/j.jphs.2017.05.003. Epub 2017 May 27.

Abstract

Kallidinogenase has been used to treat retinal vein occlusion (RVO) in patients, although there are no evidences on the effects of kallidinogenase on the retinal edema and the non-perfused areas in eyes with a RVO. We have established a murine RVO model with retinal edema and non-perfused areas. The purpose of this study was to evaluate the effects of kallidinogenase on the retinal edema and size of the non-perfused areas in the mouse RVO model. We evaluated the thickness of the retinal layers and size of the non-perfused areas, and the blood flow by laser speckle flowgraphy in RVO model. The effects of an intravenous injection of kallidinogenase on the retinal edema and size of the non-perfused areas were determined. In addition, the expressions of phosphorylated protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were measured by Western blotting. Our results showed that kallidinogenase reduced the degree of retinal edema and size of the non-perfused areas by an increase in the blood flow in RVO model. Kallidinogenase also increased the levels of phosphorylated Akt and eNOS. These findings indicate that kallidinogenase acted through Akt/eNOS-dependent phosphorylation. Thus, kallidinogenase should be considered as a possible therapeutic agent for RVO patients.

Keywords: Blood flow; Edema; Kallidinogenase; Non-perfused area; Retinal vein occlusion.

MeSH terms

  • Animals
  • Humans
  • Kallikreins / therapeutic use*
  • Male
  • Mice
  • Nitric Oxide Synthase Type III / metabolism
  • Papilledema / drug therapy*
  • Papilledema / metabolism
  • Papilledema / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Regional Blood Flow
  • Retinal Vein Occlusion / drug therapy*
  • Retinal Vein Occlusion / metabolism
  • Retinal Vein Occlusion / pathology

Substances

  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt
  • Kallikreins