| Cataracts are by far the most common cause of low visual acuity. The condition is effectively treated by surgical procedure i.e. phacoemusification or extracapsular cataract extraction (ECCE) and intraocular lens (IOL) implantation, however Posterior Capsule Opacification (PCO) is a routine complication, characterized by the formation of cloudy areas on the posterior lens capsule. This is caused by proliferation and migration of the residual lens epithelial cells (LECs) not removed during cataract surgery. There are several methods to prevent PCO which, however, involve additional risks and expense. Prevention of PCO, therefore, become an essential task for every ophthalmologist. Much effort has been made to prevent PCO by a few of methods, especially by chemical- or immune-destroying the residual LECs. However, none of these are proved to be both effective to LECs and low risk to the surrounding ocular tissues. Clinical application of these methods is currently difficult. Tranilast (N- (3',4'-dimethoxycinnamoyl)anthranilic acid), a novel anti-allergic agent, interferes with the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor and transforming growth factor beta-1. Basic and preliminary clinical studies conducted with tranilast in Japan have shown encouraging results in terms of treating the allergic conjunctivitis, and recently in preventing PCO, especially pearls or fibrosis. We demonstrate here a potential role of Tranilast on prevention of PCO which includes the following two aspects: 1. Effects of Tranilast on cultured lens epithelial cells (LECs) of rabbitsPurpose: To determine the effects of Tranilast on LECs proliferation and their growth & differentiation in cell cycle. Methods: The primary cultured rabbit LECs were treated in DMEM medium containing various concentrations of Tranilast. The number of cells was counted by Haematocytometer every day, and its growth curve was then determined. The effects of Tranilast on cell cycle of these cells was assessed by the FACS Calibur flow cytometer. The LECs were randomized into six groups: two un-treated groups (one with no Tranilast, one with 0.004% MMC) and four treated groups (various concentration of Tranilast). Results: Tranilast reduced proliferation of cultured rabbit LECs in a dose dependent manner. We found that the LECs were suppressed by Tranilast from a dose of 180 μM to 720μM . However, we did not see significant morphological changes of these cells following the treatment. A significant increase in the cell population at the G0/G1 phase of the cell cycle from 67.47% to 79% and a decrease in the population in the S phase from 21.19% to 4.32% were observed after the Tranilast treatment. The cells died 48 hours after the 0.004%MMC treatment. Conclusion: The results indicate that Tranilast is a potential inhibitor which blocks the proliferation of LECs at G1 restriction point.2. Effect of Tranilast microspheres (tranilast-MS) in preventing PCO in rabbitPurpose: To evaluate the effects of tranilast-MS on prevention of PCO after treatment with tranilast-MS on in vivo rabbit eyes. Methods: The treatment for prevention of PCO were exploited by introducing Tranilast-MS into the lens capsule bag or anterior chamber after lens content was removed, and the incidence of PCO was assessed 3 months post-treatment. Application of the treatment in lens capsule bagForty-seven rabbits' eyes were randomly divided into 8 groups: the three Tranilast-MS treated groups (2mg, 1mg, 0.5mg), the Microspheres without Tranilast treated group, the Dexamethasone treated group, the Tranilast Crystals treated group, the medium treated group, and the normal control group. A standard phacoemulsification operation was performed in all of the groups, and then followed by introducing the treatment solutions listed above, respectively. On the post-operative days of 30, 60, and 90, the animals were carried out in vivomonitoring for anterior reaction and...
|
PDF Full Text Request