PMID- 23010641
OWN - NLM
STAT- MEDLINE
DCOM- 20130115
LR  - 20121112
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 53
IP  - 12
DP  - 2012 Nov 9
TI  - Upregulation of retinal neuronal MCP-1 in the rodent model of diabetic 
      retinopathy and its function in vitro.
PG  - 7567-75
LID - 10.1167/iovs.12-9446 [doi]
AB  - PURPOSE: To evaluate the expression of monocyte chemoattractant protein-1 (MCP-1) 
      in the rodent model of diabetic retinopathy (DR) and to study the stimulation of 
      microglial activation by retinal neuronal MCP-1 in vitro. METHODS: Diabetes 
      mellitus was induced by streptozotocin (STZ) injection. The expression of MCP-1 
      was determined using immunohistochemical methods, Western blotting and RT-PCR 
      analyses. Retinal neurons and microglia were separated and co-cultured in a 
      Transwell apparatus. The levels of soluble MCP-1 that were produced after 
      stimulation of retinal neurons by adding advanced glycation end products (AGEs) 
      to the medium were measured by ELISA. The degree of microglial activation was 
      measured by testing microglial migration and the level of soluble TNF-alpha in the 
      medium by ELISA. The ability of neuronal MCP-1 to stimulate microglia activation 
      was examined by pre-exposing the retinal neurons to AGEs and an MCP-1 antibody or 
      to AGEs and SiRNA specific to MCP-1. RESULTS: A marked increase in the expression 
      of MCP-1 was detected 4 weeks after STZ injection, and the expression was 
      consistently upregulated at 3 and 5 months in the rodent DR model. Stimulation 
      with AGEs significantly increased the expression of MCP-1 in retinal neurons, 
      which activated microglial cells, including increased microglial migration and 
      upregulated secretion of TNF-alpha. Retinal neurons that were pre-exposed to AGEs and 
      an MCP-1 antibody or MCP-1 knockdown displayed greatly reduced microglial 
      migration and TNF-alpha secretion. CONCLUSIONS: Upregulation of MCP-1 began during 
      the early stage of DR and increased with the development of the disease. Retinal 
      neurons are the main source of MCP-1, and they play an important role in retinal 
      microglial activation, which may be an important link in the pathogenesis of DM.
FAU - Dong, Ning
AU  - Dong N
AD  - Department of Ophthalmology, Beijing Shijitan Hospital, Capital Medical 
      University, Beijing, People's Republic of China.
FAU - Li, Xiaoxin
AU  - Li X
FAU - Xiao, Lin
AU  - Xiao L
FAU - Yu, Wenzen
AU  - Yu W
FAU - Wang, Bingsong
AU  - Wang B
FAU - Chu, Liqun
AU  - Chu L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121109
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/*genetics
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Experimental/*genetics/metabolism/pathology
MH  - Diabetic Retinopathy/*genetics/metabolism/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - RNA, Messenger/biosynthesis/*genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Neurons/*metabolism/pathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Up-Regulation
EDAT- 2012/09/27 06:00
MHDA- 2013/01/16 06:00
CRDT- 2012/09/27 06:00
PHST- 2012/09/27 06:00 [entrez]
PHST- 2012/09/27 06:00 [pubmed]
PHST- 2013/01/16 06:00 [medline]
AID - iovs.12-9446 [pii]
AID - 10.1167/iovs.12-9446 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2012 Nov 9;53(12):7567-75. doi: 10.1167/iovs.12-9446.