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Suguru Nakagawa, Tetsuya Toyono, Takashi Minami, Tomohiko Usui; Lacking Down’s syndrome candidate region-1 lead corneal opacity via neovascularization.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1393.
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© ARVO (1962-2015); The Authors (2016-present)
Down’s syndrome candidate region (DSCR)-1 (also known as RCAN1) suppresses vascular endothelial growth factor (VEGF)-mediated angiogenesis via calcineurin-NFAT pathway in cancer. However, a role of DSCR1 in development of corneal neovascularization is unknown.
Corneal neovascularization in 20- to 24-week-old male mice of Dscr1 knockout (Dscr1-/-) mice and Dscr1 transgenic (Dscr1Tg) mice was induced by 10-0 nylon suturing. Angiogenesis were quantified using double staining with CD31. Anti-SDF1 neutral antibody administrations in Dscr1-/- mice were performed by subconjunctival injection. For genome-wide transcription analysis, Affymetrix GeneChip Mouse Genome 430 2.0 Array (Affymetrix, CA, USA) was used. The expression of DSCR-1 of human patients was examined using immunohistochemistry in Formalin-fixed paraffin-embedded (FFPE) specimens of human corneal inflammatory diseases.
Dscr1-/- mice developed spontaneous corneal opacity with age. Corneal angiogenesis were increased in the sutured cornea of Dscr1-/-mice. On the other hand, corneal angiogenesiswas decreased in the sutured cornea of Dscr1Tg mice. Pro-angiogenic Sdf1 expression was upregulated in cornea of Dscr1-/- mice and downregulated in Dscr1Tg mice. Anti- SDF1 administrations attenuated Dscr1-/--induced corneal opacities. Expression of DSCR1 was detected in blood vessels and inflammatory cells in FFPE specimens of human corneal inflammatory diseases.
We demonstrated a connection between the calcineurin inhibitor DSCR1 and corneal angiogenesis. NFAT-SDF-1/CXCR4 signaling axis would be a key regulator for corneal neovascularization.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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