J Korean Ophthalmol Soc.  2008 Dec;49(12):1981-1988.

The Effectiveness of Tranilast in the Prevention of Posterior Capsular Opacity

• Kim HY
• Lee HI
• Chun YS
• Kim JC

Abstract

PURPOSE: To evaluate the inhibitory effect of tranilast on the formation of posterior capsular opacity (PCO) after a cataract operation ex vivo and in a rabbit model.
METHODS
A human lens epithelial cell line (B3) was treated with 0.005-0.1 mM tranilast. Cytotoxicity assessment and effective dosage determination of tranilast were performed using MTT assays. B3 cell lines were cultured in Eagle's minimal essential medium (EMEM) containing 20% FBS with different concentrationsof tranilast, and morphological differences were observed. To investigate the effect of tranilast on cytokine production in B3 cell lines, cells were treated with 0.01 mM tranilast and expression profiles of cytokines were analyzed by RT-PCR. After performing phacoemulsification and intraocular lens implantation in 10 white rabbits, 0.5% tranilast eye drops were given 4 times per day, and the severity of PCO was evaluated bi-weekly using POCOman for 8 weeks after the operation.
RESULTS
Cell death was observed in the 0.05 mM tranilast-treated B3 cell lines, and inhibition of epithelial-mesenchymal transition (EMT) was also observed in the 0.01 mM tranilast-treated B3 cell lines. TGF-beta1/2, IL-18, and CDK7 mRNA expression decreased in the 0.01 mM tranilast-treated B3 cell lines. Significant suppression of PCO formation was observed in rabbits treated with 0.5% tranilast eye drops 5 weeks post operative (p<0.05).
CONCLUSIONS
The results from this study show that tranilast suppresses EMT through inhibition of TGF-beta, IL-18,and CDK7 expression. The results suggest that tranilast can be used toprevent PCO formation after cataract surgery.

Keyword

Cytokine; Epithelial-mesenchymal transition; Lens epithelial cell lines; Posterior capsular opacity; Tranilast

MeSH Terms

Cataract
Cell Death
Cell Line
Cytokines
Epithelial Cells
Epithelial-Mesenchymal Transition
Humans
Interleukin-18
Lens Implantation, Intraocular
Ophthalmic Solutions
ortho-Aminobenzoates
Phacoemulsification
Rabbits
RNA, Messenger
Transforming Growth Factor beta
Cytokines
Interleukin-18
Ophthalmic Solutions
RNA, Messenger
Transforming Growth Factor beta
ortho-Aminobenzoates

Figure

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  Figure 1. The cytotoxicity of tranilast in B3 cell lines. The rapid decrease of proliferation was found at above 0.05 mM of tranilast, which was constant regardless of the cultivation time.

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  Figure 2. Phase-contrast microscopic observation of 0.005-0.1 mM tranilast-treated B3 cell lines. Although non-treated-B3 cells showed spindle-shaped fibroblastic morphology, 0.01 mM tranilast-treated cells did not showed any morphological changes. 0.005 mM tranilast-treated cells showed slightly inhibited proliferation and morphological changes similar to non-treated cells. 0.1 mM tranilast-treated cells were detached and dead even in 1 hour after treatment.

• 

  Figure 3. Messenger RNA expression of cytokines in B3 cell lines; P=positive control 1=control group with DMSO2=0.01 mM tranilast-treatedgroup. The black arrowheads denote the prominent decrease in comparison with the control.

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  Figure 4. PCO severity grading with POCOman software. Retroilluminated picture A was transformed into a black-and-white picture B. The margin of anterior capsule should be marked then the grid is allocated automatically. Using the standard photography (grade 1-3), the severity score was calculated with the formula as follows: Severity score=(3×Red (grade3)+ 2×Yellow (grade2)+1×Blue (grade1)) / total area.

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