Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization.
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.
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Takahito
T
Nakama
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan. Electronic address: yosida@eye.med.kyushu-u.ac.jp.
Shigeo
S
Yoshida
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Keijiro
K
Ishikawa
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Yuki
Y
Kubo
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Yoshiyuki
Y
Kobayashi
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Yedi
Y
Zhou
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Shintaro
S
Nakao
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Toshio
T
Hisatomi
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Yasuhiro
Y
Ikeda
AQUA Therapeutics Co., Ltd., Kobe 650-0035, Japan.
Kazumasa
K
Takao
AQUA Therapeutics Co., Ltd., Kobe 650-0035, Japan.
Kazunori
K
Yoshikawa
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Akira
A
Matsuda
Shino-test Corporation, Sagamihara 252-0331, Japan.
Junya
J
Ono
Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga 849-8501, Japan.
Shoichiro
S
Ohta
Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga 849-8501, Japan.
Kenji
K
Izuhara
Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Akira
A
Kudo
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Koh-Hei
KH
Sonoda
Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Tatsuro
T
Ishibashi
RNAi; diabetic retinopathy; neovascularization; periostin