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

• Published in: Journal of pharmacological sciences Vol. 134; no. 2; pp. 86 - 92
• Main Authors: Nishinaka, Anri, Fuma, Shinichiro, Inoue, Yuki, Shimazawa, Masamitsu, Hara, Hideaki
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.06.2017; Elsevier
• Subjects: Animals; Blood flow; Edema; Humans; Kallidinogenase; Kallikreins - therapeutic use; Male; Mice; Nitric Oxide Synthase Type III - metabolism; Non-perfused area; Papilledema - drug therapy; Papilledema - metabolism; Papilledema - pathology; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Regional Blood Flow; Retinal vein occlusion; Retinal Vein Occlusion - drug therapy; Retinal Vein Occlusion - metabolism; Retinal Vein Occlusion - pathology; Retinal vein occlusion; Edema; Non-perfused area; Kallidinogenase; Blood flow
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2017.05.003

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.