An experimental study of rabbit conjunctival epithelial toxicity using co-treatment with Mitomycin-C and a histone deacetylase inhibitor
This study was conducted to evaluate cytotoxicity due to co-treatment with low-dose Mitomycin-C (MMC) and the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA) for glaucoma filtration surgery. In this study, the effect of co-treatment with MMC and SAHA to induce apoptosis in cultured conjunctival epithelial cells (CEs) in rabbit was investigated. The cytotoxic potential following co-treatment with MMC and SAHA in CEs via assay for reactive oxygen species (ROS) and lactate dehydrogenase (LDH) was also examined. Co-treatment with MMC and SAHA did not induce apoptosis in CEs. In addition, co-treatment with MMC and SAHA caused no significant alteration of ROS and LDH levels in CEs. This study therefore shows that low-dose MMC could still be used as an antimetabolite in co-treatment with SAHA to effectively inhibit fibrosis of Tenon’s capsule fibroblasts (TCFs) following glaucoma filtration surgery, while minimizing cytotoxicity in CEs.
Key wordsMitomycin-C Histone deacetylase inhibitor Suberoylanilide hydroxamic acid (SAHA) Apoptosis Glaucoma filtration surgery
Unable to display preview. Download preview PDF.
- Esson, D. W., Neelakantan, A., Iyer, S. A., Blalock, T. D., Balasubramanian, L., Grotendorst, G. R., Schultz, G. S., and Sherwood, M. B., Expression of Connective Tissue Growth Factor after Glaucoma Filtration Surgery in a Rabbit Model. Invest. Ophthalmol. Vis. Sci., 45, 485–491 (2004).CrossRefPubMedGoogle Scholar
- He, L. Z., Tolentino, T., Grayson, P., Zhong, S., Warrell, R. P. Jr., Rifkind, R. A., Marks, P. A., Richon, V. M., and Pandolfi, P. P., Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia. J. Clin. Invest., 108, 1321–1330 (2001).PubMedGoogle Scholar
- Jung, D. Y. and Lee, J. S., Experimental study for rabbit corneal epithelial toxicity of MMC. J. Kor. Ophthalmol. Soc., 40, 926–932 (1999).Google Scholar
- Kim, M. S., Kwon, H. J., Lee, Y. M., Baek, J. H., Jang, J. E., Lee, S. W., Moon, E. J., Kim, H. S., Lee, S. K., Chung, H. Y., Kim, C. W., and Kim, K. W., Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat. Med., 7, 437–443 (2001).CrossRefPubMedGoogle Scholar
- Kim, T. H., Kim, S. W., Woo, J. M., Rho, J. H., Lee, D. J., Park, J. M., Jeong, W. J., Park, W. C., Yoo, Y. H., and Rho, S. H., Co-treatment of suberoylanilide hydroxamic acid and mitomycin-C induces the apoptosis of rabbit tenon’s capsule fibroblast and improves the outcome of glaucoma filtration surgery. Curr. Eye Res., 33, 237–245 (2008).CrossRefPubMedGoogle Scholar
- Kronfeld, P. C., The mechanism of filtering operations. Trans. Pacific Coast Oto. Ophthalmol. Soc. Annu. Meet., 30, 23–40 (1949).Google Scholar
- Lee, S. H. and Kim, C. M., Filtering operation with adjunctive mitomycin-C in rabbit: Comparative study by subconjunctival injection and soaking of mitomycin-c. J. Kor. Ophthalmol. Soc., 37, 1700–1708 (1996).Google Scholar