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.
OBJECTIVE
This study was undertaken to develop a new treatment modality that would be able to minimize fibrosis and provide better outcome with glaucoma filtration surgery (GFS).


METHODS
We examined whether co-treatment with mitomycin-C (MMC) and histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) efficiently induces apoptosis on rabbit Tenon's capsule fibroblasts (TCF) in vitro. We further examined the effect of co-treatment with SAHA and MMC on the alteration of IOP and the bleb survival in rabbits following GFS.


RESULTS
Co-treatment of MMC and SAHA efficiently induces apoptosis in TCFs via the up-regulation of p53 and increased phosphorylation of p53 on serine 15 and 392. Also, co-treatment of SAHA and low-dose MMC decreases IOP, prolongs bleb survival, and induces apoptosis of cells under the bleb area following GFS.


CONCLUSIONS
This study shows that a co-treatment of SAHA and MMC could improve the outcome of GFS.
Kim
Tae Hyun
TH
Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, Busan, South Korea.
Kim
Sang Woo
SW
Woo
Jung Min
JM
Rho
Jee Hyun
JH
Lee
Dong Jun
DJ
Park
Jung Min
JM
Jeong
Woo Jin
WJ
Park
Woo Chan
WC
Yoo
Young Hyun
YH
Rho
Sae Heun
SH
D000477:Alkylating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D003239:Connective Tissue Cells / Q000187:drug effects; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis / Q000517:prevention & control; D018463:Filtering Surgery; D019084:Fluorescent Antibody Technique, Indirect; D005901:Glaucoma / Q000601:surgery*; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007429:Intraocular Pressure / Q000187:drug effects; D016685:Mitomycin / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation; D011817:Rabbits; D013524:Surgical Flaps; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D000077337:Vorinostat; D051025:bcl-Associated Death Protein / Q000378:metabolism
D000477:Alkylating Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016159:Tumor Suppressor Protein p53; D051025:bcl-Associated Death Protein; D016685:Mitomycin; D000077337:Vorinostat; D053148:Caspase 3