PMID- 28709891
OWN - NLM
STAT- MEDLINE
DCOM- 20170901
LR  - 20181212
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 162
DP  - 2017 Sep
TI  - Neuroprotective effects of methyl 3,4 dihydroxybenzoate in a mouse model of 
      retinitis pigmentosa.
PG  - 86-96
LID - S0014-4835(17)30234-8 [pii]
LID - 10.1016/j.exer.2017.07.004 [doi]
AB  - Retinitis pigmentosa is a photoreceptor-degenerative disease that is currently 
      untreatable and eventually causes blindness. Methyl 3,4 dihydroxybenzoate (MDHB) 
      is a small molecule that exerts neuroprotective effects in vitro. The present 
      study tests whether MDHB protects the retina of rd10 mice, a model of retinitis 
      pigmentosa. MDHB or an equal volume of vehicle was intraperitoneally injected in 
      rd10 mice daily from postnatal day 12 (P12) to P26. Retinal morphology was 
      evaluated by immunostaining, and retinal function by electroretinogram (ERG) and 
      by visual behavior. TUNEL, Iba1, GFAP staining and western blotting were applied 
      to explore the neuroprotective mechanism of MDHB in retina. MDHB treatment 
      significantly promoted photoreceptor survival and preserved cone morphology 
      compared to the untreated animals. The visual behavior and ERG responses were 
      also greatly enhanced in MDHB-treated rd10 mice. Mechanistically, following MDHB 
      treatment, the number of TUNEL-positive cells was decreased in rd10 retina, and 
      the expression of brain-derived neurotrophic factor (BDNF) protein and 
      phosphorylated tropomyosin-related kinase B (TrkB) receptor were increased. 
      Furthermore, blocking TrkB using the antagonist ANA-12 prevented the protective 
      effect of MDHB on photoreceptor survival and structure. MDHB treatment also 
      inhibited microglial activation and Muller cell gliosis in rd10 retina. In 
      conclusion, MDHB treatment delays retinal degeneration in rd10 mice and preserves 
      retinal structure and functions. These effects are likely mediated by the 
      BDNF-TrkB pathway. Due to its neurotrophic effects and ability to reduce reactive 
      gliosis, MDHB may be useful to treat degenerative diseases in retina and brain.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Zhang, Jia
AU  - Zhang J
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International 
      Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan 
      University, Guangzhou 510632, China.
FAU - Xu, Di
AU  - Xu D
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International 
      Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan 
      University, Guangzhou 510632, China.
FAU - Ouyang, Huan
AU  - Ouyang H
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International 
      Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan 
      University, Guangzhou 510632, China.
FAU - Hu, Songhui
AU  - Hu S
AD  - Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 
      China.
FAU - Li, Ang
AU  - Li A
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International 
      Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan 
      University, Guangzhou 510632, China.
FAU - Luo, Huanmin
AU  - Luo H
AD  - Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 
      China. Electronic address: tlhm@jnu.edu.cn.
FAU - Xu, Ying
AU  - Xu Y
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Joint International 
      Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan 
      University, Guangzhou 510632, China; Changsha Academician Expert Workstation, 
      Aier Eye Hospital Group, Changsha, China; Co-Innovation Center of 
      Neuroregeneration, Nantong University, Jiangsu, China. Electronic address: 
      xuying@jnu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170711
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Hydroxybenzoates)
RN  - 0 (Neuroprotective Agents)
RN  - G72J90268X (methyl 3,4-dihydroxybenzoate)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Survival
MH  - Disease Models, Animal
MH  - Electroretinography
MH  - Hydroxybenzoates/*pharmacology
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*pharmacology
MH  - Retinal Cone Photoreceptor Cells/drug effects/metabolism/*pathology
MH  - Retinitis Pigmentosa/*drug therapy/metabolism/pathology
OTO - NOTNLM
OT  - Apoptosis
OT  - BDNF
OT  - Photoreceptor
OT  - Retinitis pigmentosa
OT  - TrkB
EDAT- 2017/07/16 06:00
MHDA- 2017/09/02 06:00
CRDT- 2017/07/16 06:00
PHST- 2017/03/28 00:00 [received]
PHST- 2017/06/24 00:00 [revised]
PHST- 2017/07/10 00:00 [accepted]
PHST- 2017/07/16 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2017/07/16 06:00 [entrez]
AID - S0014-4835(17)30234-8 [pii]
AID - 10.1016/j.exer.2017.07.004 [doi]
PST - ppublish
SO  - Exp Eye Res. 2017 Sep;162:86-96. doi: 10.1016/j.exer.2017.07.004. Epub 2017 Jul 
      11.