title: The role of Nod1 signaling in corneal neovascularization.
abstract: OBJECTIVE
  Corneal neovascularization (CNV) is associated with Chlamydia trachomatis. The minimal components of bacterial cell walls are recognized by nucleotide-binding oligomerization domain-containing protein (Nod), which is important for host defense--a mechanism manifested in human corneal cells. We aimed to examine whether Nod stimulation is associated with CNV.
  
  
  METHODS
  Three groups of mice with alkali-induced CNV were topically treated with tripeptide L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP, a Nod1 agonist), muramyl dipeptide (a Nod2 agonist), or phosphate-buffered saline twice daily for 8 days. The time course responses were quantified using biomicroscopic examinations and immunohistochemistry. Angiogenic factor expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. To confirm the involvement of Nod1 signaling in CNV, RICK (an essential molecule in Nod signaling)-knockout mice treated with Tri-DAP were examined biomicroscopically and immunohistochemically 8 days after injury.
  
  
  RESULTS
  According to the biomicroscopic camera images and histology, Tri-DAP and muramyl dipeptide promoted CNV. Significantly, Tri-DAP increased the number and size of the neovascularized areas. The messenger RNA expression level of vascular endothelial growth factor was elevated in the Tri-DAP-treated mice after alkali injury. Compared with wild-type mice, CNV was attenuated in RICK-deficient mice treated with Tri-DAP.
  
  
  CONCLUSIONS
  These data suggest that Nod1 stimulation is an important inducer of CNV and that Nod1 might be useful in the development of CNV therapies.
authors: Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Korea.
authors: Sung J
authors: SJ
authors: Kim
authors: Ji W
authors: JW
authors: Lee
authors: Eui-do
authors: ED
authors: Yeo
authors: Seong-Lan
authors: SL
authors: Yu
authors: Woo-Sean
authors: WS
authors: Jean
authors: Jeong-Hwan
authors: JH
authors: Kim
authors: Chang-Gyo
authors: CG
authors: Park
authors: Hoi Y
authors: HY
authors: Lee
authors: Seung-Yun
authors: SY
authors: Han
authors: Jong-Hwan
authors: JH
authors: Park
authors: Byung-Yi
authors: BY
authors: Ko
authors: Jaeku
authors: J
authors: Kang
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000627:therapeutic use; D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy / Q000378:metabolism*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000819:agonists / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000502:physiology; D009842:Oligopeptides / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C555437:L-Ala-gamma-D-Glu-meso-diaminopimelic acid; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse