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Anti-neovascular effect of chondrocyte-derived extracellular matrix on corneal alkaline burns in rabbits

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Abstract

Purpose

We investigated the effect of a chondrocyte-derived extracellular matrix (CDECM) on experimental corneal alkaline burns in rabbits.

Methods

Corneal neovascularization (NV) was induced by applying an 8-mm filter paper soaked in 1 N NaOH to the right central corneas of rabbits for 1 minute. Ten days later, the rabbits were randomly divided into three groups: the alkaline burn group, the CDECM transplantation group, and the human amniotic membrane (HAM) transplantation group. The left eyes were used as controls. CDECM and HAM were transplanted onto the corneal surface to completely cover the resected area and were subsequently sutured. On the 10th day after transplantation, the structural changes of the cornea were analyzed histologically. We examined the effects of CDECM on clinical NV features and on the expression of corneal NV markers.

Results

The alkaline burn produced significant NV and increased the corneal thickness. On day 10 after transplantation, the thickness, NV and opacity of the cornea were markedly decreased in the CDECM group (p < 0.001). However, the HAM transplantation group did not exhibit improvements in these clinical parameters, and there were no significant differences relative to the burn group. In addition, the use of CDECM improved the healing of the cornea following the alkaline burn by disrupting the corneal epithelial proliferation and reducing the fibrotic changes of the stroma. The hallmarks of NV were significantly induced in the subepithelium by the alkaline burn, and these levels were also suppressed by CDECM. The CDECM suppressed corneal NV by inhibiting nuclear factor-kappa B (NF-κB) activation by blocking the PKC and Akt signaling pathways.

Conclusions

CDECM transplantation was markedly effective in healing alkali-burned corneas by modulating the translocation of NF-κB to the nucleus, thereby representing a promising material for the noninvasive treatment of ocular surface disease.

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Financial support

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare Affairs, Republic of Korea (grant #: HI12C0005).

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The authors indicate no potential conflicts of interest.

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Correspondence to Jae Wook Yang.

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Author contributions

H.S. Lee: conception and design; data analysis and interpretation; manuscript writing. J.H. Lee: data analysis and interpretation. C.E. Kim: data analysis and interpretation. J.W. Yang: conception and design; financial support; manuscript writing; final approval manuscript.

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Lee, H.S., Lee, J.H., Kim, C.E. et al. Anti-neovascular effect of chondrocyte-derived extracellular matrix on corneal alkaline burns in rabbits. Graefes Arch Clin Exp Ophthalmol 252, 951–961 (2014). https://doi.org/10.1007/s00417-014-2633-3

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  • DOI: https://doi.org/10.1007/s00417-014-2633-3

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