The Evaluation of Human Tenon’s Fibroblasts and Endothelial Cell Responses to Antifibrotics Alone and in Combination with α-Tocopherol

Abstract

Purpose: We aimed to evaluate the influence of current antifibrotic agents as well as the possible results obtained by combining these agents. This study included α-tocopherol, a strong antifibrotic and an efficient neuromediator of pathways used by other agents.

Materials and Methods: Mitochondrial Bcl-2, Bax, cytochrome c and cytoplasmic caspase-3 expression, as well as toxic effect patterns, mitosis and cellular reactions due to α-tocopherol alone or combined with paclitaxel, mitomycin C and 5-flurouracil (5-FU), was studied in series obtained from human endothelial and primary Tenon’s fibroblast cell cultures.

Results: The strongest apoptotic effect in both cell groups belonged to paclitaxel, followed by mitomycin C, and despite the overall suppressive effect of the α-tocopherol combination, mitomycin C increased its efficiency on the endothelial cells. The apoptosis/necrosis ratio was highest in α-tocopherol and lowest in paclitaxel, with α-tocopherol generally decreasing necrosis. Bax was observed at a high level with mitomycin C. Cytotoxicity was the highest with paclitaxel, and the caspase-3 reaction was markedly higher with mitomycin C in both cell types. In the α-tocopherol and 5-FU slides, mitosis and a layered formation were observed. The addition of α-tocopherol reduced the cytotoxicity of all antifibrotic agents in both cell series by decreasing the cell numbers, leading to necrosis.

Conclusions: Alone or in combination, the use of α-tocopherol and 5-FU is safer than other agents. By suppressing the cytotoxic effects of other antifibrotic agents, α-tocopherol is a promising drug for improving the effects of antifibrotics in many aspects of medicine. In addition, it has the potential to play a role beyond its antioxidant and antifibrotic activity in ocular surgery.

• α-tocopherol
• 5-fluorouracil
• antifibrotic
• apoptosis
• endothelium
• glaucoma surgery
• Tenon's fibroblast
• mitomycin

Acknowledgements

Authors wish to thank Jonathan G. Crowston, professor and director of Glaucoma Research, University of Melbourne, Australia, for sharing his precious experiences with patience and generosity, throughout the primary human Tenon’s fibroblast culture process in this study.

Declaration of interest

None of the authors had any financial support or relationships that may pose conflict of interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.