PMID- 32072884
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20210609
IS  - 1875-5631 (Electronic)
IS  - 1566-5232 (Linking)
VI  - 19
IP  - 6
DP  - 2020
TI  - Effect of Proteasome Inhibitors on the AAV-Mediated Transduction Efficiency in 
      Retinal Bipolar Cells.
PG  - 404-412
LID - 10.2174/1566523220666200211111326 [doi]
AB  - BACKGROUND: Adeno-associated Virus (AAV) vectors are the most promising vehicles 
      for therapeutic gene delivery to the retina. To develop a practical gene delivery 
      tool, achieving high AAV transduction efficiency in specific cell types is often 
      required. AAV-mediated targeted expression in retinal bipolar cells is needed in 
      certain applications such as optogenetic therapy, however, the transduction 
      efficiency driven by endogenous cell-specific promoters is usually low. Methods 
      that can improve AAV transduction efficiency in bipolar cells need to be 
      developed. OBJECTIVE: The study aimed to examine the effect of proteasome 
      inhibitors on AAV-mediated transduction efficiency in retinal bipolar cells. 
      METHODS: Quantitative analysis of fluorescent reporter protein expression was 
      performed to assess the effect of two proteasome inhibitors, doxorubicin and 
      MG132, on AAV-mediated transduction efficiency in retinal bipolar cells in mice. 
      RESULTS: Our results showed that doxorubicin can increase the AAV transduction 
      efficiency in retinal bipolar cells in a dose-dependent manner. We also observed 
      doxorubicin-mediated cytotoxicity in retinal neurons, but the cytotoxicity could 
      be mitigated by the coapplication of dexrazoxane. Three months after the 
      coapplication of doxorubicin (300 muM) and dexrazoxane, the AAV transduction 
      efficiency in retinal bipolar cells increased by 33.8% and no cytotoxicity was 
      observed in all the layers of the retina. CONCLUSION: Doxorubicin could enhance 
      the AAV transduction efficiency in retinal bipolar cells in vivo. The potential 
      long-term cytotoxicity caused by doxorubicin to retinal neurons could be 
      partially mitigated by dexrazoxane. The coapplication of doxorubicin and 
      dexrazoxane may serve as a potential adjuvant regimen for improving AAV 
      transduction efficiency in retinal bipolar cells.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Cui, Shengjie
AU  - Cui S
AD  - Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State 
      University, School of Medicine, Detroit, MI, 48201, United States.
FAU - Ganjawala, Tushar H
AU  - Ganjawala TH
AD  - Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State 
      University, School of Medicine, Detroit, MI, 48201, United States.
FAU - Abrams, Gary W
AU  - Abrams GW
AD  - Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State 
      University, School of Medicine, Detroit, MI, 48201, United States.
FAU - Pan, Zhuo-Hua
AU  - Pan ZH
AD  - Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State 
      University, School of Medicine, Detroit, MI, 48201, United States.
LA  - eng
GR  - P30 EY004068/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Gene Ther
JT  - Current gene therapy
JID - 101125446
RN  - 0 (Leupeptins)
RN  - 0 (Proteasome Inhibitors)
RN  - 048L81261F (Dexrazoxane)
RN  - 80168379AG (Doxorubicin)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Animals
MH  - Dependovirus/genetics
MH  - Dexrazoxane/pharmacology
MH  - Doxorubicin/pharmacology
MH  - Gene Expression/*drug effects
MH  - Genetic Vectors
MH  - Leupeptins/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Proteasome Inhibitors/*pharmacology
MH  - Retina/metabolism/virology
MH  - Retinal Bipolar Cells/*drug effects/*metabolism/virology
MH  - Retinal Ganglion Cells/metabolism/virology
MH  - Transduction, Genetic/methods
OTO - NOTNLM
OT  - Adeno-associated virus
OT  - bipolar cells
OT  - dexrazoxane
OT  - doxorubicin
OT  - retina
OT  - retinal gene therapy.
EDAT- 2020/02/20 06:00
MHDA- 2021/06/10 06:00
CRDT- 2020/02/20 06:00
PHST- 2019/11/21 00:00 [received]
PHST- 2020/01/29 00:00 [revised]
PHST- 2020/01/30 00:00 [accepted]
PHST- 2020/02/20 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
PHST- 2020/02/20 06:00 [entrez]
AID - CGT-EPUB-104384 [pii]
AID - 10.2174/1566523220666200211111326 [doi]
PST - ppublish
SO  - Curr Gene Ther. 2020;19(6):404-412. doi: 10.2174/1566523220666200211111326.