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Published on: April 6, 2022
An experimental study of rabbit conjunctival epithelial toxicity using co-treatment with mitomycin-C and a histone
Tae-Hyun Kim1, Hyun Cheol Oh, Young Hyun Yoo
1Department Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, Busan, 602-714, Korea.
Abstract:
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.
Insights
Low-dose Mitomycin-C (MMC) combined with suberoylanilide hydroxamic acid (SAHA) does not induce apoptosis or significant cytotoxicity in ocular cells. This finding supports their use in glaucoma surgery to prevent fibrosis with minimal cell damage.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Glaucoma filtration surgery aims to reduce intraocular pressure but is often complicated by fibrosis.
- Mitomycin-C (MMC) and suberoylanilide hydroxamic acid (SAHA) are investigated for antifibrotic effects.
- Evaluating the cytotoxicity of combined MMC and SAHA on ocular cells is crucial for surgical safety.
Purpose of the Study:
- To assess the cytotoxic effects of co-administering low-dose Mitomycin-C (MMC) and suberoylanilide hydroxamic acid (SAHA) on rabbit conjunctival epithelial cells (CEs).
- To investigate the potential of this combination therapy to induce apoptosis and alter reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels in CEs.
- To determine the safety profile of combined MMC and SAHA for use in glaucoma filtration surgery.
Main Methods:
- Cultured rabbit conjunctival epithelial cells (CEs) were treated with low-dose Mitomycin-C (MMC) and suberoylanilide hydroxamic acid (SAHA).
- Apoptosis was evaluated using specific cellular assays.
- Cytotoxicity was assessed by measuring reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels.
Main Results:
- Co-treatment with MMC and SAHA did not induce apoptosis in conjunctival epithelial cells (CEs).
- No significant alterations in reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels were observed.
- The combination therapy demonstrated minimal cytotoxicity in CEs.
Conclusions:
- Low-dose Mitomycin-C (MMC) can be safely co-administered with suberoylanilide hydroxamic acid (SAHA) in glaucoma filtration surgery.
- This combination effectively inhibits Tenon's capsule fibroblast (TCF) fibrosis while maintaining a low cytotoxicity profile.
- The findings support the use of combined MMC and SAHA as an antifibrotic strategy in glaucoma surgery.
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