PMID- 28692738
OWN - NLM
STAT- MEDLINE
DCOM- 20170714
LR  - 20180216
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 9
DP  - 2017 Jul 1
TI  - Inhibition of Monocyte Chemoattractant Protein 1 Prevents Conjunctival Fibrosis 
      in an Experimental Model of Glaucoma Filtration Surgery.
PG  - 3432-3439
LID - 10.1167/iovs.17-21480 [doi]
AB  - PURPOSE: To evaluate the effect of treatment with monocyte chemoattractant 
      protein-1 receptor inhibitor (MCP-Ri) to maintain bleb survival and prevent 
      fibrosis in an experimental model of glaucoma filtration surgery (GFS). METHODS: 
      GFS was performed on one eye of C57/Bl6 mice (n = 36) that was treated with 
      MCP-Ri, mitomycin-C (MMC), or vehicle at the time of surgery. Real-time 
      polymerase chain reaction was used to evaluate conjunctival expression of 
      monocyte chemoattractant protein-1 (MCP-1), TGFB1, TGFB2, collagen 1a1 (Col1a1), 
      sparc (Sparc), and fibronectin at 2 and 7 days following surgery. Anterior 
      segment slit-lamp examination, optical coherence tomography, and confocal 
      microscopy were performed in vivo at day 14. Eyes were processed for 
      immunohistochemical staining of F4/80, a monocyte-macrophage marker, at day 2. In 
      vitro experiments were also performed to compare the effect of MMC, MCP-Ri, and 
      vehicle on the viability of mouse Tenon's fibroblasts. RESULTS: Treatment with 
      MCP-Ri results in a greater reduction in the percentage of F4/80-positive cells 
      in conjunctival blebs and lesser MCP-1 gene expression following experimental GFS 
      than MMC or control. Both MMC and MCP-Ri reduced Col1a1 and Sparc expression, but 
      not fibronectin. TGFB1 decreased with MCP-Ri but not MMC; MMC but not MCP-Ri 
      reduced TGFB2. MMC and MCP-Ri treatment resulted in the preservation of bleb 
      height at day 14, as compared to control. MCP-Ri was less toxic to mouse Tenon's 
      fibroblasts in comparison with MMC. CONCLUSIONS: Targeting MCP-1 results in 
      prolonged bleb survival following experimental GFS with less cellular toxicity as 
      compared to MMC. MCP inhibition could provide a safer alternative to conventional 
      antifibrotic adjunctive treatments in GFS.
FAU - Chong, Rachel Shujuan
AU  - Chong RS
AD  - Singapore National Eye Centre, Singapore 2Singapore Eye Research Institute, 
      Singapore 3Duke NUS Graduate Medical School, Singapore.
FAU - Lee, Ying Shi
AU  - Lee YS
AD  - Singapore Eye Research Institute, Singapore.
FAU - Chu, Stephanie Wai Ling
AU  - Chu SWL
AD  - Singapore Eye Research Institute, Singapore.
FAU - Toh, Li Zhen
AU  - Toh LZ
AD  - Singapore Eye Research Institute, Singapore.
FAU - Wong, Tina Tzee Ling
AU  - Wong TTL
AD  - Singapore National Eye Centre, Singapore 2Singapore Eye Research Institute, 
      Singapore 3Duke NUS Graduate Medical School, Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Antifibrinolytic Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fibronectins)
RN  - 0 (Osteonectin)
RN  - 0 (Receptors, CCR2)
RN  - 0 (SPARC protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 50SG953SK6 (Mitomycin)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Antifibrinolytic Agents/*pharmacology
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/*antagonists & inhibitors/metabolism
MH  - Collagen/metabolism
MH  - Conjunctiva/*drug effects
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/*pharmacology
MH  - Fibroblasts/*drug effects
MH  - Fibronectins/metabolism
MH  - Fibrosis/*prevention & control
MH  - Filtering Surgery
MH  - Glaucoma/*drug therapy/surgery
MH  - *Glaucoma Drainage Implants
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitomycin/pharmacokinetics
MH  - Osteonectin/metabolism
MH  - Receptors, CCR2/*antagonists & inhibitors
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2017/07/12 06:00
MHDA- 2017/07/15 06:00
CRDT- 2017/07/11 06:00
PHST- 2017/07/11 06:00 [entrez]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2017/07/15 06:00 [medline]
AID - 2643580 [pii]
AID - 10.1167/iovs.17-21480 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Jul 1;58(9):3432-3439. doi: 
      10.1167/iovs.17-21480.