PMID- 28918027
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210109
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 8
DP  - 2017 Sep 15
TI  - Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin RNA 
      Suppresses Laser-Induced Choroidal Neovascularization.
PG  - 26-35
LID - S2162-2531(17)30183-X [pii]
LID - 10.1016/j.omtn.2017.05.012 [doi]
AB  - Choroidal neovascularization (CNV) is the defining characteristic feature of the 
      wet subtype of age-related macular degeneration (AMD) and may result in 
      irreversible blindness. Based on anti-vascular endothelial growth factor 
      (anti-VEGF), the current therapeutic approaches to CNV are fraught with 
      difficulties, and mammalian target of rapamycin (mTOR) has recently been proposed 
      as a possible therapeutic target, although few studies have been conducted. Here, 
      we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short 
      hairpin RNA (rAAV-mTOR shRNA), which blocks the activity of both mTOR complex 1 
      and 2, represents a promising therapeutic approach for the treatment of CNV. 
      Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA) 
      after generating CNV lesions in the eyes via laser photocoagulation. The 
      recombinant adeno-associated virus (rAAV) delivery vehicle was able to 
      effectively transduce cells in the inner retina, and significantly fewer 
      inflammatory cells and less extensive CNV were observed in the animals treated 
      with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated 
      groups. Presumably related to the reduction of CNV, increased autophagy was 
      detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer 
      apoptotic cells detected in the outer nuclear layer around the CNV indicate that 
      mTOR inhibition may also have neuroprotective effects. Taken together, these 
      results demonstrate the therapeutic potential of mTOR inhibition, resulting from 
      rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV.
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Park, Tae Kwann
AU  - Park TK
AD  - Department of Ophthalmology, Soonchunhyang University, College of Medicine, 
      Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang 
      University Hospital Bucheon, Bucheon 14584, Republic of Korea. Electronic 
      address: tkpark@schmc.ac.kr.
FAU - Lee, Si Hyung
AU  - Lee SH
AD  - Department of Ophthalmology, Soonchunhyang University, College of Medicine, 
      Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang 
      University Hospital Bucheon, Bucheon 14584, Republic of Korea.
FAU - Choi, Jun Sub
AU  - Choi JS
AD  - Cdmogen Co., Ltd., Cheongju 28751, Republic of Korea.
FAU - Nah, Seung Kwan
AU  - Nah SK
AD  - Department of Ophthalmology, Soonchunhyang University, College of Medicine, 
      Cheonan 31151, Republic of Korea; Department of Ophthalmology, Soonchunhyang 
      University Hospital Bucheon, Bucheon 14584, Republic of Korea.
FAU - Kim, Hee Jong
AU  - Kim HJ
AD  - Cdmogen Co., Ltd., Cheongju 28751, Republic of Korea.
FAU - Park, Ha Yan
AU  - Park HY
AD  - Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 
      14584, Republic of Korea.
FAU - Lee, Heuiran
AU  - Lee H
AD  - Department of Microbiology, Cellular Dysfunction Research Center, Asan Medical 
      Center, University of Ulsan, College of Medicine, Seoul 05505, Republic of Korea.
FAU - Lee, Steven Hyun Seung
AU  - Lee SHS
AD  - Department of Microbiology, Cellular Dysfunction Research Center, Asan Medical 
      Center, University of Ulsan, College of Medicine, Seoul 05505, Republic of Korea.
FAU - Park, Keerang
AU  - Park K
AD  - Department of Biopharmacy, Chungbuk Health & Science University, Cheongju, 
      Chungbuk 28150, Republic of Korea. Electronic address: krpark@chsu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20170601
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC5477068
OTO - NOTNLM
OT  - RNA interference
OT  - adeno-associated virus
OT  - autophagy
OT  - choroidal neovascularization
OT  - mTOR
OT  - mTOR shRNA
OT  - retinal neovascularization
EDAT- 2017/09/18 06:00
MHDA- 2017/09/18 06:01
PMCR- 2017/06/01
CRDT- 2017/09/18 06:00
PHST- 2017/02/08 00:00 [received]
PHST- 2017/05/29 00:00 [revised]
PHST- 2017/05/29 00:00 [accepted]
PHST- 2017/09/18 06:00 [entrez]
PHST- 2017/09/18 06:00 [pubmed]
PHST- 2017/09/18 06:01 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - S2162-2531(17)30183-X [pii]
AID - 10.1016/j.omtn.2017.05.012 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2017 Sep 15;8:26-35. doi: 10.1016/j.omtn.2017.05.012. 
      Epub 2017 Jun 1.