Suppression of choroidal neovascularization in lectin-like oxidized low-density lipoprotein receptor type 1-deficient mice.
OBJECTIVE
To elucidate the role of the scavenger receptor, lectin-like oxidized low-density lipoprotein receptor type 1 (LOX-1), in the formation of choroidal neovascularization (CNV).


METHODS
CNV was induced by laser photocoagulation of the ocular fundus in mice. The expression of LOX-1 mRNA and protein after laser injury was determined by real-time RT-PCR and Western blot analysis. Gelatin zymography was used to measure the activity of matrix metalloproteinase (MMP)-2 and pro-MMP-9, and ELISA was used to determine monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF) levels. At 14 days after laser injury, the extent of CNV was evaluated by fluorescein angiography and lectin staining using confocal microscopy.


RESULTS
In wild-type mice, the relative expression level of LOX-1 mRNA compared with the control increased significantly 6 hours after laser injury and peaked 12 hours after laser injury (P = 0.011 and P = 0.0006, respectively), and the expression of LOX-1 protein was also detected 1 and 3 days after laser injury. Increases in MMP-2, pro-MMP2, and pro-MMP-9 after laser injury were reduced in LOX-1-deficient mice compared with wild-type mice. At 3 days after laser injury, increases in MCP-1 and VEGF significantly decreased in LOX-1-deficient mice compared with wild-type mice (P = 0.014 and P = 0.001, respectively). Morphometric analyses revealed that the induction of CNV formation was significantly inhibited in LOX-1-deficient mice.


CONCLUSIONS
These results suggest that LOX-1 plays an important role in the formation of CNV. This scavenging system might thus be a novel therapeutic target for CNV.
Inomata
Yasuya
Y
Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. inoyas@kxb.biglobe.ne.jp
Fukushima
Mikiko
M
Hara
Ryuhei
R
Takahashi
Eri
E
Honjo
Megumi
M
Koga
Takahisa
T
Kawaji
Takahiro
T
Satoh
Hiroo
H
Takeya
Motohiro
M
Sawamura
Tatsuya
T
Tanihara
Hidenobu
H
D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004792:Enzyme Precursors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000172:deficiency / Q000502:physiology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004792:Enzyme Precursors; C495138:Olr1 protein, mouse; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C120487:pro-matrix metalloproteinase 9; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9