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Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in
Eyes with Retinal Neovascularization
#MMPMID28325294
Nakama T
; Yoshida S
; Ishikawa K
; Kubo Y
; Kobayashi Y
; Zhou Y
; Nakao S
; Hisatomi T
; Ikeda Y
; Takao K
; Yoshikawa K
; Matsuda A
; Ono J
; Ohta S
; Izuhara K
; Kudo A
; Sonoda KH
; Ishibashi T
Mol Ther Nucleic Acids
2017[Mar]; 6
(?): 279-289
PMID28325294
show ga
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
?v?3. 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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