TY - JOUR
T1 - Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization
AU - Nakama, Takahito
AU - Yoshida, Shigeo
AU - Ishikawa, Keijiro
AU - Kubo, Yuki
AU - Kobayashi, Yoshiyuki
AU - Zhou, Yedi
AU - Nakao, Shintaro
AU - Hisatomi, Toshio
AU - Ikeda, Yasuhiro
AU - Takao, Kazumasa
AU - Yoshikawa, Kazunori
AU - Matsuda, Akira
AU - Ono, Junya
AU - Ohta, Shoichiro
AU - Izuhara, Kenji
AU - Kudo, Akira
AU - Sonoda, Koh hei
AU - Ishibashi, Tatsuro
N1 - Funding Information:
The authors thank Masayo Eto, Kinuko Sasada, and Hiroko Miura for their excellent technical assistance. This work was supported in part by JSPS KAKENHI grants 26293374, 26670757, and 15H04995, and Takeda Science Foundation. T.N. is supported by a fellowship from The Japan Society for the Promotion of Science for Young Scientists.
Publisher Copyright:
© 2017
PY - 2017/3/17
Y1 - 2017/3/17
N2 - Retinal neovascularization (NV) due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN) may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs) in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.
AB - Retinal neovascularization (NV) due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN) may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs) in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.
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U2 - 10.1016/j.omtn.2017.01.004
DO - 10.1016/j.omtn.2017.01.004
M3 - Article
AN - SCOPUS:85015687459
SN - 2162-2531
VL - 6
SP - 279
EP - 289
JO - Molecular Therapy - Nucleic Acids
JF - Molecular Therapy - Nucleic Acids
ER -
