The role of Nod1 signaling in corneal neovascularization.

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. 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. 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. These data suggest that Nod1 stimulation is an important inducer of CNV and that Nod1 might be useful in the development of CNV therapies.

Citation

Sung J Kim, Ji W Lee, Eui-do Yeo, Seong-Lan Yu, Woo-Sean Jean, Jeong-Hwan Kim, Chang-Gyo Park, Hoi Y Lee, Seung-Yun Han, Jong-Hwan Park, Byung-Yi Ko, Jaeku Kang. The role of Nod1 signaling in corneal neovascularization. Cornea. 2013 May;32(5):674-9

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PMID: 23328697

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