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Deniz Hos, Marie-Luise Dreisow, Franziska Bucher, Birgit Regenfuss, Felix Bock, Claus Cursiefen; Interleukin-10 regulates corneal lymphangiogenesis and the resolution of inflammatory responses . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4505.
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© ARVO (1962-2015); The Authors (2016-present)
Aim of this study was to investigate whether Interleukin-10 (IL-10), an anti-inflammatory and immune-modulatory cytokine, is involved in the regulation of corneal hem- and lymphangiogenesis and inflammation.
IL-10 mRNA and protein expression was analyzed in healthy and inflamed murine corneas after suture placement. The in vitro effect of IL-10 on inflammatory and (lymph)angiogenic growth factor expression by macrophages (peritoneal exudate cells, PECs) was assessed by real-time PCR. Furthermore, suture placement was performed in wildtype (wt) and IL-10 deficient (IL-10 -/-) mice. Afterwards, corneal inflammatory and (lymph)angiogenic growth factor expression, corneal hem- and lymphangiogenesis and inflammatory cell numbers were determined.
IL-10 mRNA was not measurable in healthy corneas. However, in inflamed corneas, IL-10 mRNA and protein were detectable. IL-10 was expressed by CD11b+ cells. IL-10 stimulation reduced IL-1ß, TNF-α and VEGF-A expression in PECs, whereas VEGF-C expression was significantly upregulated. VEGF-D expression remained unaltered. After suture placement, IL-10 -/- mice showed similar hemvascularized areas, whereas lymphvascularized areas were reduced when compared to wt. Consistently, IL-10 -/- mice showed an increase in corneal VEGF-A levels after suture placement that was comparable to wt, whereas the increase in corneal VEGF-C and -D expression levels was significantly lower in IL-10 -/- mice compared to wt. IL-1ß and TNF-α expression increased to significantly higher levels in IL-10 -/- mice compared to wt after suture placement, which was also accompanied by higher corneal CD11b+ cell numbers. Moreover, inflammatory cytokine expression and CD11b+ cell numbers in IL-10 -/- mice persisted on significantly higher levels even after the removal of corneal sutures.
IL-10 regulates corneal lymphangiogenesis, presumably via macrophage derived growth factor expression. Furthermore, reduced corneal lymphangiogenesis in IL-10 -/- mice is associated with more intense and prolonged inflammation, indicating a possible role of IL-10 and lymphatic vessels in the regulation and resolution of inflammatory corneal responses.
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