PMID- 28432360
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Apr 21
TI  - Functional ectopic neuritogenesis by retinal rod bipolar cells is regulated by 
      miR-125b-5p during retinal remodeling in RCS rats.
PG  - 1011
LID - 10.1038/s41598-017-01261-x [doi]
LID - 1011
AB  - Following retinal degeneration, retinal remodeling can cause neuronal 
      microcircuits to undergo structural alterations, which particularly affect the 
      dendrites of bipolar cells. However, the mechanisms and functional consequences 
      of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats 
      as a model of retinal degeneration, to study structural changes in rod bipolar 
      cells (RBCs) and the underlying mechanisms of these changes. We found that, with 
      retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL) 
      of the retina, and the ectopic dendrites formed synapses with the remaining 
      photoreceptors. This ectopic neuritogenesis was associated with brain-derived 
      neurotrophic factor (BDNF) - expression of which was negatively regulated by 
      miR-125b-5p. Overexpression of miR-125b-5p in the retinae of RCS rats diminished 
      RBC ectopic dendrites, and compromised the b-wave of the flash electroretinogram 
      (ERG). In contrast, down-regulation of miR-125b-5p (or exogenous BDNF treatment) 
      increased RBC ectopic dendrites, and improved b-wave. Furthermore, we showed that 
      the regulation of ectopic neuritogenesis by BDNF occurred via the downstream 
      modulation of the TrkB-CREB signaling pathway. Based on these findings, we 
      conclude that ectopic dendrites are likely to be providing functional benefits 
      and that, in RCS rats, miR-125b-5p regulates ectopic neuritogenesis by RBCs 
      through modulation of the BDNF-TrkB-CREB pathway. This suggests that therapies 
      that reduce miR-125b-5p expression could be beneficial in human retinal 
      degenerative disease.
FAU - Fu, Yan
AU  - Fu Y
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China.
FAU - Hou, Baoke
AU  - Hou B
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China.
FAU - Weng, Chuanhuang
AU  - Weng C
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China.
FAU - Liu, Weiping
AU  - Liu W
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China.
FAU - Dai, Jiaman
AU  - Dai J
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China.
FAU - Zhao, Congjian
AU  - Zhao C
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China. cj.zhao@yahoo.com.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China. cj.zhao@yahoo.com.
FAU - Yin, Zheng Qin
AU  - Yin ZQ
AD  - Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, 
      Chongqing, 400038, China. qinzyin@aliyun.com.
AD  - Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 
      400038, China. qinzyin@aliyun.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170421
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn125 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Dendrites/*metabolism
MH  - Disease Models, Animal
MH  - Electroretinography
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - Rats
MH  - Retinal Bipolar Cells/*cytology/pathology
MH  - Retinal Degeneration/genetics/*pathology
MH  - Retinal Rod Photoreceptor Cells/cytology/pathology
PMC - PMC5430652
COIS- The authors declare that they have no competing interests.
EDAT- 2017/04/23 06:00
MHDA- 2018/09/19 06:00
PMCR- 2017/04/21
CRDT- 2017/04/23 06:00
PHST- 2016/07/27 00:00 [received]
PHST- 2017/03/24 00:00 [accepted]
PHST- 2017/04/23 06:00 [entrez]
PHST- 2017/04/23 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2017/04/21 00:00 [pmc-release]
AID - 10.1038/s41598-017-01261-x [pii]
AID - 1261 [pii]
AID - 10.1038/s41598-017-01261-x [doi]
PST - epublish
SO  - Sci Rep. 2017 Apr 21;7(1):1011. doi: 10.1038/s41598-017-01261-x.